UK Biobank
English
Biobank
数据描述
UK Biobank is a large-scale biomedical database and research resource containing de-identified genetic, lifestyle, and health information alongside biological samples from approximately 500,000 UK participants. The dataset is designed to support health-related research in the public interest by enabling approved researchers worldwide to analyse rich participant data through a secure, cloud-based platform. It is used to investigate prevention, diagnosis, and treatment across a wide range of serious diseases, including cancer, heart disease, and stroke, and to drive new discoveries that can improve public health.
www.ukbiobank.ac.uk
IP: 51.140.85.106
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相关论文
687Multi-ancestry genome-wide association and integrated multi-omics analyses of endometriosis and its clinical manifestations
Dora Koller•Jun He•Solveig Løkhammer•Selena Aranda•Dan Qiu等 17 人
Nature Genetics
2026
•2026/4/29
•00 p.1-11
Endometriosis is a chronic systemic disease affecting ~10% of women, yet its genetic basis and molecular mechanisms remain poorly understood. Hence, here we conducted a genome-wide association study of endometriosis and adenomyosis in ~1.4 million women, including 105,869 cases, aiming to expand loc...
Genetics researchGenome-wide association studiesReproductive disorders
10.1038/S41588-026-02582-2
ISSN:1061-4036
The genetic architecture of multimodal human brain age
Junhao Wen•Bingxin Zhao•Zhijian Yang•Guray Erus•Ioanna Skampardoni等 18 人
Nature Communications
2024
•2024/3/23
•Vol.15 No.1 p.1-15
The complex biological mechanisms underlying human brain aging remain incompletely understood. This study investigated the genetic architecture of three brain age gaps (BAG) derived from gray matter volume (GM-BAG), white matter microstructure (WM-BAG), and functional connectivity (FC-BAG). We ident...
Genetics researchMachine learningPredictive markers
10.1038/S41467-024-46796-6
ISSN:2041-1723
Genome-wide association study unravels mechanisms of brain glymphatic activity
Shu-Yi Huang•Yi-Jun Ge•Peng Ren•Bang-Sheng Wu•Weikang Gong等 20 人
Nature Communications
2025
•2025/1/13
•Vol.16 No.1 p.1-17
Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significa...
Diseases of the nervous systemGenetics of the nervous systemNeurological disordersNeurology
10.1038/S41467-024-55706-9
ISSN:2041-1723
A resampling-based approach to share reference panels
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Nature Computational Science
2024
•2024/5/14
•00 p.1-7
For many genome-wide association studies, imputing genotypes from a haplotype reference panel is a necessary step. Over the past 15 years, reference panels have become larger and more diverse, leading to improvements in imputation accuracy. However, the latest generation of reference panels is subje...
DNA sequencingGenome-wide association studiesHaplotypes
10.1038/S43588-024-00630-7
ISSN:2662-8457
Brain aging patterns in a large and diverse cohort of 49,482 individuals
Zhijian Yang•Junhao Wen•Guray Erus•Sindhuja T. Govindarajan•Randa Melhem等 53 人
Nature Medicine
2024
•2024/8/15
•00 p.1-12
Brain aging process is influenced by various lifestyle, environmental and genetic factors, as well as by age-related and often coexisting pathologies. Magnetic resonance imaging and artificial intelligence methods have been instrumental in understanding neuroanatomical changes that occur during agin...
Brain imagingEngineeringNeurological disordersPrognostic markers
10.1038/S41591-024-03144-X
ISSN:1078-8956
Machine learning-assisted optimization of dietary intervention against dementia risk
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Nature Human Behaviour
2025
•2025/7/2
•00 p.1-14
A healthy diet has been associated with a reduced risk of dementia. Here we devised a Machine learning-assisted Optimizing Dietary intERvention against demeNtia risk (MODERN) diet based on data from 185,012 UK Biobank participants, 1,987 of whom developed all-cause dementia over 10 years. We first i...
DementiaDiseases of the nervous systemRisk factors
10.1038/S41562-025-02255-W
ISSN:2397-3374
Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation
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Nature Communications
2024
•2024/3/18
•Vol.15 No.1 p.1-14
There is currently no medical therapy to prevent calcific aortic valve stenosis (CAVS). Multi-omics approaches could lead to the identification of novel molecular targets. Here, we perform a genome-wide association study (GWAS) meta-analysis including 14,819 cases among 941,863 participants of Europ...
Cardiovascular geneticsGene expressionGenome-wide association studies
10.1038/S41467-024-46639-4
ISSN:2041-1723
Integrated multiomics of pressure overload in the human heart prioritizes targets relevant to heart failure
Brian R. Lindman•Andrew S. Perry•Michelle L. Lance•Kaushik Amancherla•Namju Kim等 31 人
Nature Communications
2025
•2025/7/26
•Vol.16 No.1 p.1-16
Pressure overload initiates a series of alterations in the human heart that predate macroscopic organ-level remodeling and downstream heart failure. We study aortic stenosis through integrated proteomic, tissue transcriptomic, and genetic methods to prioritize targets causal in human heart failure. ...
BiomarkersCardiologyMolecular medicine
10.1038/S41467-025-62201-2
ISSN:2041-1723
Dose-response relationship between accelerometer-measured physical activity and depression: evidence from the UK Biobank
Shuangfa Qu•Zhenhua Xing
Translational Psychiatry
2025
•2025/8/19
•Vol.15 No.1 p.1-8
Studies on the relationship between physical activity (PA) and depression often rely on self-reported data, with a predominant focus on moderate-to-vigorous physical activity (MVPA). However, research examining accelerometer-measured PA, particularly light physical activity (LPA), and its impact on ...
DepressionPredictive markers
10.1038/S41398-025-03543-9
ISSN:2158-3188
Positive predictive value highlights four novel candidates for actionable genetic screening from analysis of 220,000 clinicogenomic records
Schiabor Barrett Kelly M.•Bolze Alexandre•Ni Yunyun•White Simon•Isaksson Magnus等 12 人
Genetics In Medicine
2021
•2021/8/13
•00 p.1-9
To identify conditions that are candidates for population genetic screening based on population prevalence, penetrance of rare variants, and actionability. We analyzed exome and medical record data from >220,000 participants across two large population health cohorts with different demographics. We ...
Biomedicine, generalHuman GeneticsLaboratory Medicine
10.1038/S41436-021-01293-9
ISSN:1098-3600
A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis
Steven Bell•Andreas S. Rigas•Magnus K. Magnusson•Egil Ferkingstad•Elias Allara等 61 人
Communications Biology
2021
•2021/2/3
•Vol.4 No.1 p.1-14
Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430)...
Genetic variationGenetics research
10.1038/S42003-020-01575-Z
ISSN:2399-3642
A resource-efficient tool for mixed model association analysis of large-scale data
Longda Jiang•Zhili Zheng•Ting Qi•Kathryn E. Kemper•Naomi R. Wray等 7 人
Nature Genetics
2019
•2019/11/25
•Vol.51 No.12 p.1749-1755
The genome-wide association study (GWAS) has been widely used as an experimental design to detect associations between genetic variants and a phenotype. Two major confounding factors, population stratification and relatedness, could potentially lead to inflated GWAS test statistics and hence to spur...
Genome-wide association studiesSoftware
10.1038/S41588-019-0530-8
ISSN:1061-4036
Genome-wide polygenic score to predict chronic kidney disease across ancestries
Khan Atlas•Turchin Michael C.•Patki Amit•Srinivasasainagendra Vinodh•Shang Ning等 39 人
Nature Medicine
2022
•2022/6/16
•00 p.1-9
Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality. Polygenic prediction could enhance CKD screening and prevention; however, this approach has not been optimized for ancestrally diverse populations. By combining APOL1 risk genotypes with genome-w...
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10.1038/S41591-022-01869-1
ISSN:1078-8956
UK Biobank study of the association between circadian syndrome and cardio-kidney events or all-cause mortality
Hong-Juan Yang•Hong Shu•Rui Chen•Qian Hou•Jia-Xin Huang等 8 人
Communications Medicine
2025
•2025/9/24
•Vol.5 No.1 p.1-8
Circadian syndrome (CircS) has demonstrated a strong association with the occurrence of cardiovascular disease (CVD), as well as chronic kidney disease (CKD). However, the association of CircS with cardiac-kidney events (CKE) or even mortality is unknown. This study was to evaluate whether CircS was...
Cardiovascular diseasesChronic kidney diseaseMetabolic syndrome
10.1038/S43856-025-01064-6
ISSN:2730-664X
Proteomic risk score for early prediction of kidney disease progression in individuals with APOL1 high-risk genotypes
Chenyu Li•Shola M. Richards•Ghazal Quinn•Amin Abedini•Minyan Zhu等 24 人
Nature Medicine
2026
•2026/4/15
•00 p.1-7
Individuals of African ancestry carrying APOL1 (apolipoprotein L1) high-risk genotypes face a markedly increased risk of kidney failure, yet tools to identify those individuals likely to progress to chronic kidney disease are lacking. Here we profiled plasma proteomes of 851 Penn Medicine BioBank pa...
Chronic kidney diseasePredictive markers
10.1038/S41591-026-04337-2
ISSN:1078-8956
Human lifespan changes in the brain’s functional connectome
Lianglong Sun•Tengda Zhao•Xinyuan Liang•Mingrui Xia•Qiongling Li等 69 人
Nature Neuroscience
2025
•2025/4/3
•Vol.28 No.4 p.891-901
Functional connectivity of the human brain changes through life. Here, we assemble task-free functional and structural magnetic resonance imaging data from 33,250 individuals at 32 weeks of postmenstrual age to 80 years from 132 global sites. We report critical inflection points in the nonlinear gro...
Cognitive neuroscienceFunctional magnetic resonance imaging
10.1038/S41593-025-01907-4
ISSN:1097-6256
Sequence variants associated with BMI affect disease risk through BMI itself
Gudmundur Einarsson•Gudmar Thorleifsson•Valgerdur Steinthorsdottir•Florian Zink•Hannes Helgason等 31 人
Nature Communications
2024
•2024/11/12
•Vol.15 No.1 p.1-9
Mendelian Randomization studies indicate that BMI contributes to various diseases, but it’s unclear if this is entirely mediated by BMI itself. This study examines whether disease risk from BMI-associated sequence variants is mediated through BMI or other mechanisms, using data from Iceland and the ...
Genetic association studyPopulation geneticsRisk factors
10.1038/S41467-024-53568-9
ISSN:2041-1723
Improved analyses of GWAS summary statistics by reducing data heterogeneity and errors
Chen Wenhan•Wu Yang•Zheng Zhili•Qi Ting•Visscher Peter M.等 7 人
Nature Communications
2021
•2021/12/8
•Vol.12 No.1 p.1-10
Summary statistics from genome-wide association studies (GWAS) have facilitated the development of various summary data-based methods, which typically require a reference sample for linkage disequilibrium (LD) estimation. Analyses using these methods may be biased by errors in GWAS summary data or L...
Genome-wide association studiesQuality controlSoftware
10.1038/S41467-021-27438-7
ISSN:2041-1723
Shared and distinct genetic etiologies for different types of clonal hematopoiesis
Derek W. Brown•Liam D. Cato•Yajie Zhao•Satish K. Nandakumar•Erik L. Bao等 15 人
Nature Communications
2023
•2023/9/8
•Vol.14 No.1 p.1-13
Clonal hematopoiesis (CH)—age-related expansion of mutated hematopoietic clones—can differ in frequency and cellular fitness by CH type (e.g., mutations in driver genes (CHIP), gains/losses and copy-neutral loss of chromosomal segments (mCAs), and loss of sex chromosomes). Co-occurring CH raises que...
EpidemiologyGenetics research
10.1038/S41467-023-41315-5
ISSN:2041-1723
Comparing DXA and MRI body composition measurements in cross-sectional and longitudinal cohorts
Nicolas Basty•Marjola Thanaj•Brandon Whitcher•Jimmy D. Bell•E. Louise Thomas
Communications Medicine
2026
•2026/3/5
0Detailed body composition assessment, through measurement of adipose tissue and muscle distribution, is essential for understanding population health trends, guiding targeted interventions, evaluating lifestyle effects, and monitoring age-related changes such as sarcopenia. Dual X-ray absorptiometry...
Magnetic resonance imagingMedical imagingWhole body imaging
10.1038/S43856-026-01440-W
ISSN:2730-664X
Genetic underpinnings of risky behaviour relate to altered neuroanatomy
Gökhan Aydogan•Remi Daviet•Richard Karlsson Linnér•Todd A. Hare•Joseph W. Kable等 10 人
Nature Human Behaviour
2021
•2021/1/28
•00 p.1-8
Previous research points to the heritability of risk-taking behaviour. However, evidence on how genetic dispositions are translated into risky behaviour is scarce. Here, we report a genetically informed neuroimaging study of real-world risky behaviour across the domains of drinking, smoking, driving...
Behavioural geneticsDecisionEconomicsHuman behaviourReward
10.1038/S41562-020-01027-Y
ISSN:2397-3374
Neck-to-knee dixon MRI thigh volume as a superior mass biomarker for Sarcopenia: evidence from the UK biobank
Hyeon Su Kim•Hyunwoo Park•Junseok Kang•Hyunbin Kim•Bonsang Gu等 7 人
Npj Digital Medicine
2026
•2026/2/5
•Vol.9 No.1 p.2390
Sarcopenia assessment requires biomarkers capturing muscle-specific strength beyond single-slice measurements. We developed an automated MRI framework segmenting 27 pelvic–thigh musculoskeletal structures to investigate muscle distribution as functional biomarkers. Among 37,004 UK Biobank participan...
BiomarkersDiseasesHealth careMedical research
10.1038/S41746-026-02379-X
ISSN:2398-6352
A prospective study of associations between accelerated biological aging and twenty musculoskeletal disorders
Wenming Wei•Xin Qi•Bolun Cheng•Na Zhang•Yijing Zhao等 20 人
Communications Medicine
2024
•2024/12/18
•Vol.4 No.1 p.1-8
Musculoskeletal disorders pose major public health challenges, and accelerated biological aging may increase their risk. This study investigates the association between biological aging and musculoskeletal disorders, with a focus on sex-related differences. We analyzed data from 172,332 UK Biobank p...
Predictive markersRheumatic diseases
10.1038/S43856-024-00706-5
ISSN:2730-664X
Circulating causal protein networks linked to future risk of myocardial infarction
Sean Bankier•Valborg Gudmundsdottir•Thorarinn Jonmundsson•Heida Bjarnadottir•Joseph Loureiro等 17 人
Nature Communications
2025
•2025/12/18
0Variations in blood protein levels have been linked to numerous complex diseases, including cardiovascular conditions. These associations highlight the intricate interplay between local and systemic factors in cardiovascular disease development, emphasizing the need for a comprehensive, systems-leve...
Computational biology and bioinformaticsMolecular medicine
10.1038/S41467-025-67135-3
ISSN:2041-1723
Complex patterns of multimorbidity associated with severe COVID-19 and long COVID
Maik Pietzner•Spiros Denaxas•Summaira Yasmeen•Maria A. Ulmer•Tomoko Nakanishi等 9 人
Communications Medicine
2024
•2024/7/8
•Vol.4 No.1 p.1-11
Early evidence that patients with (multiple) pre-existing diseases are at highest risk for severe COVID-19 has been instrumental in the pandemic to allocate critical care resources and later vaccination schemes. However, systematic studies exploring the breadth of medical diagnoses are scarce but ma...
EpidemiologyInfectious diseases
10.1038/S43856-024-00506-X
ISSN:2730-664X
Metabolomic signature of ultraprocessed food consumption and microvascular complications among individuals with type 2 diabetes
Yue Li•Xingyue Song•Dan Xue•Yuwei Lai•Yan-Bo Zhang等 11 人
Npj Science Of Food
2025
•2025/11/17
•Vol.9 No.1 p.2330
Ultra-processed food (UPF) consumption has been associated with higher risks of diabetic microvascular complications. However, whether a metabolite profile related to UPF consumption reflects these associations was unknown. Using data from the UK Biobank (a prospective cohort study), a metabolomic s...
DiseasesEndocrine system and metabolic diseasesEndocrinologyRisk factors
10.1038/S41538-025-00597-3
ISSN:2396-8370
Metformin use on the risks of depression and anxiety in people with type 2 diabetes
Meijuan Kang•Huan Liu•Jingni Hui•Yifan Gou•Ruixue Zhou等 14 人
Communications Medicine
2025
•2025/7/22
•Vol.5 No.1 p.1-8
Many studies have shown that metformin may benefit mental health, but its genetic relevance remains unclear. The balance between metformin’s mental benefits and potential side effects has not been thoroughly explored. This highlights the need for a detailed evaluation of metformin’s impact on person...
AnxietyDepressionType 2 diabetes
10.1038/S43856-025-01006-2
ISSN:2730-664X
Association of circadian rhythms with brain disorder incidents: a prospective cohort study of 72242 participants
Chen Si-Jia•Deng Yue-Ting•Li Yu-Zhu•Zhang Ya-Ru•Zhang Wei等 12 人
Translational Psychiatry
2022
•2022/12/14
•Vol.12 No.1 p.1-9
Circadian rhythm disruption (CRD) is a shared characteristic of various brain disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and major depression disorder (MDD). Disruption of circadian rhythm might be a risk factor for brain disorder incidents. From 7-day accelerometry data ...
DepressionPsychiatric disorders
10.1038/S41398-022-02278-1
ISSN:2158-3188
Individual characteristics outperform resting-state fMRI for the prediction of behavioral phenotypes
Amir Omidvarnia•Leonard Sasse•Daouia I. Larabi•Federico Raimondo•Felix Hoffstaedter等 12 人
Communications Biology
2024
•2024/6/26
•Vol.7 No.1 p.1-12
In this study, we aimed to compare imaging-based features of brain function, measured by resting-state fMRI (rsfMRI), with individual characteristics such as age, gender, and total intracranial volume to predict behavioral measures. We developed a machine learning framework based on rsfMRI features ...
Functional magnetic resonance imagingHuman behaviourMachine learning
10.1038/S42003-024-06438-5
ISSN:2399-3642
Plasma proteome profiling identifies novel biomarkers and predictors for schizophrenia
Songyu Wu•Xinru Guo•Tingyi Jia•Zhouyang Sun•Ge Yu等 8 人
Translational Psychiatry
2026
•2026/4/4
0This study performed a systematic investigation through proteomic and longitudinal follow-up data from the UK Biobank (comprising 70 schizophrenia cases and 36,135 healthy controls) to reveal the association between protein biomarkers and the onset of schizophrenia in order to provide insights into ...
Predictive markersSchizophrenia
10.1038/S41398-026-04017-2
ISSN:2158-3188
Social isolation and the risk of Parkinson disease in the UK biobank study
Tingting Geng•Yaqi Li•Yinshun Peng•Xiao Chen•Xinming Xu等 8 人
Npj Parkinson's Disease
2024
•2024/4/8
•Vol.10 No.1 p.1-7
Parkinson disease (PD) has become one of the most rapidly growing causes of disability among the older population and social isolation is a major concern in the PD community. However, the relationship between social isolation and future risk of PD remains unclear. This study included 192,340 partici...
Parkinson's diseaseRisk factors
10.1038/S41531-024-00700-7
ISSN:2373-8057
Sugar rationing during the first 1000 days of life and lifelong risk of heart failure
Haoxian Tang•Xuan Zhang•Jingtao Huang•Xiaojing Chen•Jianan Hong等 18 人
Nature Communications
2026
•2026/1/21
•Vol.17 No.1 p.18940
Elevated sugar intake has been linked to poor cardiovascular health, but the effects of early-life sugar restriction on the lifelong risk of heart failure remain unclear. Using the end of sugar rationing in the United Kingdom in 1953 as a natural experiment, we classify participants in the UK Bioban...
CardiologyRisk factors
10.1038/S41467-026-68713-9
ISSN:2041-1723
Adding salt to foods increases the risk of metabolic dysfunction-associated steatotic liver disease
Han Chen•Xujun Zhang•Shujuan Lin•Qiong Wu
Communications Medicine
2025
•2025/8/8
•Vol.5 No.1 p.1-11
Although salt intake has been linked to multiple cardiometabolic diseases, whether the frequency of adding salt to foods, a reasonable proxy for long-term salt intake, is related to metabolic dysfunction-associated steatotic liver disease (MASLD) incidence remains unknown. This prospective study inc...
EpidemiologyNon-alcoholic fatty liver disease
10.1038/S43856-025-01074-4
ISSN:2730-664X
Associations between skeletal muscle strength and chronic kidney disease in patients with MASLD
Xin-Lei Zhang•Yeqing Gu•Jing Zhao•Pei-Wu Zhu•Wen-Ying Chen等 15 人
Communications Medicine
2025
•2025/4/16
•Vol.5 No.1 p.1-9
A skeletal muscle strength (SMS) decline is associated with metabolic diseases, but whether SMS also declines with chronic kidney disease (CKD) in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) is uncertain. This study examined the associations between SMS and the ...
Chronic kidney diseaseNon-alcoholic fatty liver disease
10.1038/S43856-025-00821-X
ISSN:2730-664X
Genetic underpinnings and causal effects of brain structure and function on chronic pain intensity
Xiuzhi Wang•Jinyu Liu•Xichen Wang•Jin Yang•Yipeng Le等 13 人
Nature Communications
2025
•2025/11/12
•Vol.16 No.1 p.99580
Chronic pain represents a major clinical burden, with its intensity being a key measure of its severity. However, the genetic and neural underpinnings of chronic pain intensity remain unraveled. Here, we identified six genetic loci (including a novel discovery) significantly associated with chronic ...
Chronic painGenome-wide association studiesNeurological disorders
10.1038/S41467-025-64904-Y
ISSN:2041-1723
Estimating direct and indirect genetic effects on offspring phenotypes using genome-wide summary results data
Warrington Nicole M.•Hwang Liang-Dar•Nivard Michel G.•Evans David M.
Nature Communications
2021
•2021/9/14
•Vol.12 No.1 p.1-12
Estimation of direct and indirect (i.e. parental and/or sibling) genetic effects on phenotypes is becoming increasingly important. We compare several multivariate methods that utilize summary results statistics from genome-wide association studies to determine how well they estimate direct and indir...
Genome-wide association studiesPopulation geneticsQuantitative trait
10.1038/S41467-021-25723-Z
ISSN:2041-1723
Reciprocal causation mixture model for robust Mendelian randomization analysis using genome-scale summary data
Liu Zipeng•Qin Yiming•Wu Tian•Tubbs Justin D.•Baum Larry等 9 人
Nature Communications
2023
•2023/2/28
•Vol.14 No.1 p.1-12
Mendelian randomization using GWAS summary statistics has become a popular method to infer causal relationships across complex diseases. However, the widespread pleiotropy observed in GWAS has made the selection of valid instrumental variables problematic, leading to possible violations of Mendelian...
DiseasesGenome-wide association studiesStatistical methods
10.1038/S41467-023-36490-4
ISSN:2041-1723
Reduced penetrance of COL1A1/2 pathogenic variants linked with osteogenesis imperfecta: analysis of a large population cohort
Alistair T. Pagnamenta•James Fasham•Robin N. Beaumont•Duncan Baker•Sylvia Keigwin等 10 人
European Journal Of Human Genetics
2026
•2026/5/12
•00 p.1-9
Osteogenesis imperfecta (OI) is under consideration for inclusion in several genomic newborn screening initiatives, but its penetrance in clinically-unselected populations is currently unknown. It is an exemplar condition for evaluating penetrance in adult cohorts due to its relatively low mortality...
Diagnostic markersDisease geneticsDiseasesGenetic testingMedical genomics
10.1038/S41431-026-02118-6
ISSN:1018-4813
MRI-based multi-organ clocks for healthy aging and disease assessment
Huizi Cao•Zhiyuan Song•Michael R. Duggan•Guray Erus•Dhivya Srinivasan等 15 人
Nature Medicine
2025
•2025/10/16
•00 p.1-11
Biological aging clocks across organ systems and tissues have advanced understanding of human aging and disease. In this study, we expand this framework to develop seven magnetic resonance imaging-based multi-organ biological age gaps (MRIBAGs), including the brain, heart, liver, adipose tissue, spl...
Data miningGenetics researchPredictive markers
10.1038/S41591-025-03999-8
ISSN:1078-8956
Fine-mapping causal tissues and genes at disease-associated loci
Benjamin J. Strober•Martin Jinye Zhang•Tiffany Amariuta•Jordan Rossen•Alkes L. Price
Nature Genetics
2025
•2025/1/2
•00 p.1-11
Complex diseases often have distinct mechanisms spanning multiple tissues. We propose tissue–gene fine-mapping (TGFM), which infers the posterior inclusion probability (PIP) for each gene–tissue pair to mediate a disease locus by analyzing summary statistics and expression quantitative trait loci (e...
Gene regulationGenome-wide association studiesSoftware
10.1038/S41588-024-01994-2
ISSN:1061-4036
Aging and increased cancer risk: exploring the potential of LE8 score to mitigate risk
Jiehui Li•Yuhan Zhang•Wenxing Zhang•Jiabin Zheng•Sheng Yu等 11 人
Npj Aging
2026
•2026/3/3
•Vol.12 No.1 p.530
Given global population aging and the absence of aging-reversal therapies, elucidating the aging-related cancer risk association and developing cancer prevention strategies are imperative. This population-based cohort study analyzed data from the UK Biobank. Aging was assessed through four validated...
BiomarkersCancerDiseasesOncologyRisk factors
10.1038/S41514-026-00352-2
ISSN:2731-6068
Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation
Anders Mälarstig•Felix Grassmann•Leo Dahl•Marios Dimitriou•Dianna McLeod等 19 人
Nature Communications
2023
•2023/11/24
•Vol.14 No.1 p.1-9
Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 ...
Breast cancerGenome-wide association studiesProteomicsTarget identification
10.1038/S41467-023-43485-8
ISSN:2041-1723
Genetic analysis of the PCSK9 locus in psychological, psychiatric, metabolic and cardiovascular traits in UK Biobank
Hay Rachel•Cullen Breda•Graham Nicholas•Lyall Donald M.•Aman Alisha等 9 人
European Journal Of Human Genetics
2022
•2022/5/2
•00 p.1-11
The association between severe mental illness (SMI) and cardiovascular and metabolic disease (CMD) is poorly understood. PCSK9 is expressed in systems critical to both SMI and CMD and influences lipid homeostasis and brain function. We systematically investigated relationships between genetic variat...
Cardiovascular diseasesGeneticsMolecular biologyPsychiatric disordersRisk factors
10.1038/S41431-022-01107-9
ISSN:1018-4813
Frailty-related plasma metabolomic signatures predict long-term mortality risk and implicate systemic aging pathways: evidence from a prospective cohort study
Xiru Zhang•Xin Feng•Wenchao Liu•Ruiyan Liu•Qingmei Huang等 10 人
Npj Aging
2026
•2026/1/13
•Vol.12 No.1 p.280
Frailty is a common geriatric syndrome associated with increased mortality, yet its underlying biological mechanisms and potential value for early risk stratification remain inadequately understood. In this large prospective cohort of more than 260,000 UK Biobank participants with plasma metabolomic...
BiomarkersCardiologyDiseasesHealth careMedical researchRisk factors
10.1038/S41514-025-00327-9
ISSN:2731-6068
Population-specific polygenic risk scores for people of Han Chinese ancestry
Hung-Hsin Chen•Chien-Hsiun Chen•Ming-Chih Hou•Yun-Ching Fu•Ling-Hui Li等 129 人
Nature
2025
•2025/10/15
•00 p.1-10
Predicting complex disease risks on the basis of individual genomic profiles is an advancing field in human genetics1,2. However, most genetic studies have focused on populations of European ancestry, creating a global imbalance in precision medicine and underscoring the need for genomic research in...
Genetic predisposition to diseaseGenetics researchGenome-wide association studiesPersonalized medicine
10.1038/S41586-025-09350-Y
ISSN:0028-0836
A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in AFF3 associated with intellectual disability
Bharati Jadhav•Paras Garg•Joke J. F. A. van Vugt•Kristina Ibanez•Delia Gagliardi等 22 人
Nature Genetics
2024
•2024/9/23
•00 p.1-11
GC-rich tandem repeat expansions (TREs) are often associated with DNA methylation, gene silencing and folate-sensitive fragile sites, and underlie several congenital and late-onset disorders. Through a combination of DNA-methylation profiling and tandem repeat genotyping, we identified 24 methylated...
EpigenomicsGenome-wide association studiesNeurodevelopmental disorders
10.1038/S41588-024-01917-1
ISSN:1061-4036
Integration of risk factor polygenic risk score with disease polygenic risk score for disease prediction
Hyein Jung•Hae-Un Jung•Eun Ju Baek•Shin Young Kwon•Ji-One Kang等 7 人
Communications Biology
2024
•2024/2/13
•Vol.7 No.1 p.1-13
Polygenic risk score (PRS) is useful for capturing an individual’s genetic susceptibility. However, previous studies have not fully exploited the potential of the risk factor PRS (RFPRS) for disease prediction. We explored the potential of integrating disease-related RFPRSs with disease PRS to enhan...
Genetic variationRisk factors
10.1038/S42003-024-05874-7
ISSN:2399-3642
Multi-ancestry genome-wide meta-analysis identifies novel basal cell carcinoma loci and shared genetic effects with squamous cell carcinoma
Hélène Choquet•Chen Jiang•Jie Yin•Yuhree Kim•Thomas J. Hoffmann等 7 人
Communications Biology
2024
•2024/1/5
•Vol.7 No.1 p.1-10
Basal cell carcinoma (BCC) is one of the most common malignancies worldwide, yet its genetic determinants are incompletely defined. We perform a European ancestry genome-wide association (GWA) meta-analysis and a Hispanic/Latino ancestry GWA meta-analysis and meta-analyze both in a multi-ancestry GW...
Basal cell carcinomaGenome-wide association studiesSquamous cell carcinoma
10.1038/S42003-023-05753-7
ISSN:2399-3642
Genome-wide study of hair colour in UK Biobank explains most of the SNP heritability
Michael D. Morgan•Erola Pairo-Castineira•Konrad Rawlik•Oriol Canela-Xandri•Jonathan Rees等 8 人
Nature Communications
2018
•2018/12/10
•Vol.9 No.1 p.1-10
Natural hair colour within European populations is a complex genetic trait. Previous work has established that MC1R variants are the principal genetic cause of red hair colour, but with variable penetrance. Here, we have extensively mapped the genes responsible for hair colour in the white, British ...
Genetic association studyGeneticsGenome-wide association studies
10.1038/S41467-018-07691-Z
ISSN:2041-1723
Cardiovascular risk assessment characterized by proteomics in cancer survivors
Peng Wang•Yu Peng•Fubin Liu•Chao Sheng•Kexin Chen等 6 人
Communications Medicine
2026
•2026/4/7
0The classic cardiovascular disease (CVD) risk scores perform poorly in predicting CVD in cancer survivors. This study aimed to identify proteins associated with major CVDs risk and explore their roles in risk prediction for major CVDs in cancer survivors. We included 4225 cancer survivors from the U...
BiomarkersCancerCardiovascular biology
10.1038/S43856-026-01570-1
ISSN:2730-664X
Risk factors associated with age at onset of Parkinson’s disease in the UK Biobank
Yuanfeng Huang•Qian Chen•Zheng Wang•Yijing Wang•Aojie Lian等 11 人
Npj Parkinson's Disease
2024
•2024/1/2
•Vol.10 No.1 p.1-8
Substantial evidence shown that the age at onset (AAO) of Parkinson’s disease (PD) is a major determinant of clinical heterogeneity. However, the mechanisms underlying heterogeneity in the AAO remain unclear. To investigate the risk factors with the AAO of PD, a total of 3156 patients with PD from t...
Parkinson's diseaseRisk factors
10.1038/S41531-023-00623-9
ISSN:2373-8057
Genetic risk, antiseizure medications, and lifestyle factors in epilepsy-associated obesity and overweight
Jiaqi Wang•Zihua He•Sisi Shen•Tong Yi•Shengyi Liu等 10 人
International Journal Of Obesity
2026
•2026/4/6
•00 p.1-12
Obesity is common among people with epilepsy and is influenced by genetic susceptibility, lifestyle behaviours, and antiseizure medications (ASMs). How ASMs and lifestyle factors interact with genetic risk for obesity in epilepsy remains unclear. This population-based cohort study analysed UK Bioban...
ObesityWeight management
10.1038/S41366-026-02069-4
ISSN:0307-0565
Cross-phenotype relationship between opioid use disorder and suicide attempts: new evidence from polygenic association and Mendelian randomization analyses
Yunqi Huang•Dongru Chen•Albert M. Levin•Brian K. Ahmedani•Cathrine Frank等 9 人
Molecular Psychiatry
2023
•2023/6/20
•00 p.1-9
Clinical epidemiological studies have found high co-occurrence between suicide attempts (SA) and opioid use disorder (OUD). However, the patterns of correlation and causation between them are still not clear due to psychiatric confounding. To investigate their cross-phenotype relationship, we utiliz...
AddictionGenetics
10.1038/S41380-023-02124-W
ISSN:1359-4184
Tea consumption and risk of incident dementia: A prospective cohort study of 377 592 UK Biobank participants
Hu He-Ying•Wu Bang-Sheng•Ou Ya-Nan•Ma Ya-Hui•Huang Yu-Yuan等 8 人
Translational Psychiatry
2022
•2022/4/26
•Vol.12 No.1 p.1-9
As a widely consumed beverage, tea boasts diverse health benefits. Herein, we aimed to investigate the association between tea consumption and dementia risk. We conducted a prospective cohort study with 377 592 UK Biobank participants during a 9-year follow-up. Cox regression models adjusted for age...
DiseasesLong-term memory
10.1038/S41398-022-01923-Z
ISSN:2158-3188
Adherence to the EAT-Lancet Diet and Risk of Sepsis: A Prospective Cohort Study from the UK Biobank
Wenbin Nan•Qiong Huang•Baimei He•Yinglan Liu•Zhenyu Peng
Npj Science Of Food
2026
•2026/3/19
0Sepsis remains a significant global health challenge due to its high incidence, mortality, and disability. While adherence to the EAT-Lancet diet has been shown to reduce the risk of various inflammatory and metabolic diseases, its impact on sepsis is not well understood. This study aimed to investi...
BiomarkersDiseasesGeneticsMedical researchRisk factors
10.1038/S41538-026-00795-7
ISSN:2396-8370
Improving polygenic risk prediction in admixed populations by explicitly modeling ancestral-differential effects via GAUDI
Quan Sun•Bryce T. Rowland•Jiawen Chen•Anna V. Mikhaylova•Christy Avery等 18 人
Nature Communications
2024
•2024/2/3
•Vol.15 No.1 p.1-14
Polygenic risk scores (PRS) have shown successes in clinics, but most PRS methods focus only on participants with distinct primary continental ancestry without accommodating recently-admixed individuals with mosaic continental ancestry backgrounds for different segments of their genomes. Here, we de...
Genetic markersQuantitative traitStatistical methods
10.1038/S41467-024-45135-Z
ISSN:2041-1723
GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis
Shuai Yuan•Jie Chen•Jiawei Geng•Sizheng Steven Zhao•James Yarmolinsky等 12 人
Nature Communications
2025
•2025/3/12
•Vol.16 No.1 p.1-11
Sarcoidosis is a complex inflammatory disease with a strong genetic component. Here, we perform a genome-wide association study in 9755 sarcoidosis cases to identify risk loci and map associated genes. We then use transcriptome-wide association studies and enrichment analyses to explore pathways inv...
AutoimmunityGene expressionGenome-wide association studies
10.1038/S41467-025-57829-Z
ISSN:2041-1723
Adjusting for population stratification in polygenic risk score analyses: a guide for model specifications in the UK Biobank
Bochao Danae Lin•Lotta-Katrin Pries•Jim van Os•Jurjen J. Luykx•Bart P. F. Rutten等 6 人
Journal Of Human Genetics
2023
•2023/5/15
•00 p.1-4
The current study was conducted to provide a general guidance for model specifications in polygenic risk score (PRS) analyses of the UK Biobank, such as adjusting for covariates (i.e. age, sex, recruitment centers, and genetic batch) and the number of principal components (PCs) that need to be inclu...
Computational biology and bioinformaticsPopulation genetics
10.1038/S10038-023-01161-1
ISSN:1434-5161
Fine-scale population structure and widespread conservation of genetic effect sizes between human groups across traits
Sile Hu•Lino A. F. Ferreira•Sinan Shi•Garrett Hellenthal•Jonathan Marchini等 7 人
Nature Genetics
2025
•2025/2/3
•Vol.57 No.2 p.379-389
Understanding genetic differences between populations is essential for avoiding confounding in genome-wide association studies and improving polygenic score (PGS) portability. We developed a statistical pipeline to infer fine-scale Ancestry Components and applied it to UK Biobank data. Ancestry Comp...
Genome-wide association studiesMedical geneticsPopulation geneticsSoftware
10.1038/S41588-024-02035-8
ISSN:1061-4036
Applying weighted Cox regression to genome-wide association studies of time-to-event phenotypes
Ying Li•Yuzhuo Ma•He Xu•Yaoyao Sun•Min Zhu等 8 人
Nature Computational Science
2025
•2025/9/12
•00 p.1-16
With the growing availability of time-stamped electronic health records linked to genetic data in large biobanks and cohorts, time-to-event phenotypes are increasingly studied in genome-wide association studies. Although numerous Cox-regression-based methods have been proposed for a large-scale geno...
Genome-wide association studiesPopulation genetics
10.1038/S43588-025-00864-Z
ISSN:2662-8457
Variant of the lactase LCT gene explains association between milk intake and incident type 2 diabetes
Kai Luo•Guo-Chong Chen•Yanbo Zhang•Jee-Young Moon•Jiaqian Xing等 20 人
Nature Metabolism
2024
•2024/1/22
•Vol.6 No.1 p.169-186
Cow’s milk is frequently included in the human diet, but the relationship between milk intake and type 2 diabetes (T2D) remains controversial. Here, using data from the Hispanic Community Health Study/Study of Latinos, we show that in both sexes, higher milk intake is associated with lower risk of T...
EpidemiologyType 2 diabetes
10.1038/S42255-023-00961-1
ISSN:2522-5812
Telomere attrition becomes an instrument for clonal selection in aging hematopoiesis and leukemogenesis
Matthew A. McLoughlin•Sruthi Cheloor Kovilakam•William G. Dunn•Muxin Gu•Jake Tobin等 47 人
Nature Genetics
2025
•2025/8/28
•00 p.1-11
The mechanisms through which mutations in splicing factor genes drive clonal hematopoiesis (CH) and myeloid malignancies, and their close association with advanced age, remain poorly understood. Here we show that telomere maintenance plays an important role in this phenomenon. First, by studying 454...
AgeingGenetics researchHaematological cancer
10.1038/S41588-025-02296-X
ISSN:1061-4036
Disease clusters subsequent to anxiety and stress-related disorders and their genetic determinants
Xin Han•Qing Shen•Can Hou•Huazhen Yang•Wenwen Chen等 12 人
Nature Communications
2024
•2024/2/8
•Vol.15 No.1 p.1-13
Anxiety/stress-related disorders have been associated with multiple diseases, whereas a comprehensive assessment of the structure and interplay of subsequent associated diseases and their genetic underpinnings is lacking. Here, we first identify 136, out of 454 tested, medical conditions associated ...
EpidemiologyPsychiatric disorders
10.1038/S41467-024-45445-2
ISSN:2041-1723
Plasma proteomic profiles linked to suicidal behaviors
Bei Zhang•Jia You•Edmund T. Rolls•Peng Ren•Yuzhu Li等 10 人
Nature Mental Health
2026
•2026/2/23
•Vol.4 No.3 p.387-399
Suicidality is a major public health concern, and characterizing plasma proteomic profiles linked to suicidal behaviors (SBs, including suicide attempt and death by suicide) offers promising avenues for developing novel therapeutic targets. In this study, leveraging data from 53,026 UK Biobank parti...
Blood proteinsPsychiatric disorders
10.1038/S44220-025-00582-5
ISSN:2731-6076
Capturing additional genetic risk from family history for improved polygenic risk prediction
Lu Tianyuan•Forgetta Vincenzo•Richards J. Brent•Greenwood Celia M. T.
Communications Biology
2022
•2022/6/16
•Vol.5 No.1 p.1-11
Family history of complex traits may reflect transmitted rare pathogenic variants, intra-familial shared exposures to environmental and lifestyle factors, as well as a common genetic predisposition. We developed a latent factor model to quantify trait heritability in excess of that captured by a com...
DiseasesPredictive medicineQuantitative traitRisk factors
10.1038/S42003-022-03532-4
ISSN:2399-3642
Shared genetic architectures of subjective well-being in East Asian and European ancestry populations
Kim Soyeon•Kim Kiwon•Hwang Mi Yeong•Ko Hyunwoong•Jung Sang-Hyuk等 19 人
Nature Human Behaviour
2022
•2022/5/19
•00 p.1-13
Subjective well-being (SWB) has been explored in European ancestral populations; however, whether the SWB genetic architecture is shared across populations remains unclear. We conducted a cross-population genome-wide association study for SWB using samples from Korean (n = 110,919) and European (n =...
GenomicsHuman behaviourQuality of life
10.1038/S41562-022-01343-5
ISSN:2397-3374
Genome-wide association study identifies susceptibility loci for acute myeloid leukemia
Lin Wei-Yu•Fordham Sarah E.•Hungate Eric•Sunter Nicola J.•Elstob Claire等 83 人
Nature Communications
2021
•2021/10/29
•Vol.12 No.1 p.1-10
Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant...
Acute myeloid leukaemiaCancer genomicsRisk factors
10.1038/S41467-021-26551-X
ISSN:2041-1723
Ambient temperature and the variability between neighbouring days impacts in-patient hospitalizations in the United Kingdom
Ka Yan Lai•Chris Webster•John Gallacher•Chinmoy Sarkar
Communications Medicine
2026
•2026/1/26
•Vol.6 No.1 p.900
Acute health effects of temperature extremes and variability in temperate zones has been rarely quantified. We examine the associations of ambient temperature and temperature change between neighbouring days with all-cause and cause-specific hospitalizations. Daily hospital admission data were ident...
Disease preventionPublic health
10.1038/S43856-025-01355-Y
ISSN:2730-664X
Exploration of first onsets of mania, schizophrenia spectrum disorders and major depressive disorder in perimenopause
Lisa M. Shitomi-Jones•Clare Dolman•Ian Jones•George Kirov•Valentina Escott-Price等 7 人
Nature Mental Health
2024
•2024/8/15
•00 p.1-8
Although the relationship between perimenopause and changes in mood has been well established, knowledge of risk of a broad spectrum of psychiatric disorders associated with reproductive aging is limited. Here we investigate whether the perimenopause (that is, the years around the final menstrual pe...
Bipolar disorderDepressionPsychosisSchizophrenia
10.1038/S44220-024-00292-4
ISSN:2731-6076
A cross-population compendium of gene–environment interactions
Shinichi Namba•Kyuto Sonehara•Yuriko N. Koyanagi•Takezo Kikuchi•Takafumi Ojima等 38 人
Nature
2026
•2026/1/28
•Vol.651 No.8106 p.688-697
Environmental differences in genetic effect sizes, namely, gene–environment interactions, may uncover the genetic encoding of phenotypic plasticity1–3. We provide a cross-population atlas of gene–environment interactions comprising 440,210 individuals from European and Japanese populations, with rep...
EpidemiologyGenetics researchGenome-wide association studiesRisk factors
10.1038/S41586-025-10054-6
ISSN:0028-0836
Multi-organ AI endophenotypes chart the heterogeneity of brain, eye and heart pan-disease
Aleix Boquet-Pujadas•Filippos Anagnostakis•Zhijian Yang•Ye Ella Tian•Michael R. Duggan等 14 人
Nature Mental Health
2026
•2026/1/6
•Vol.4 No.2 p.203-230
Disease heterogeneity and commonality pose critical challenges to precision medicine, as traditional approaches frequently focus on single disease entities and overlook shared mechanisms across conditions. Here, inspired by pan-cancer and multi-organ research, we introduce the concept of ‘pan-diseas...
Computational modelsGenetics research
10.1038/S44220-025-00560-X
ISSN:2731-6076
AI framework for multidisease detection via retinal imaging
Xiayin Zhang•Qinyi Li•Yinhao Liang•Chunran Lai•Jiahui Cao等 27 人
Nature Medicine
2026
•2026/4/28
•00 p.1-10
The rising burden of endocrine and metabolic diseases demands scalable and accessible screening tools. Here we developed Reti-Pioneer, a multitask retinal imaging framework that integrates quality-aware modules with pre-trained foundation models for efficient, multidisease detection. In general, the...
Endocrine system and metabolic diseasesMedical imagingTranslational research
10.1038/S41591-026-04359-W
ISSN:1078-8956
Phenotypic and genetic characteristics of retinal vascular parameters and their association with diseases
Sofía Ortín Vela•Michael J. Beyeler•Olga Trofimova•Ilaria Iuliani•Jose D. Vargas Quiros等 16 人
Nature Communications
2024
•2024/11/6
•Vol.15 No.1 p.1-17
Fundus images allow for non-invasive assessment of the retinal vasculature whose features provide important information on health. Using a fully automated image processing pipeline, we extract 17 different morphological vascular phenotypes, including median vessels diameter, diameter variability, ma...
Cardiovascular biologyGenetic variationGenome-wide association studies
10.1038/S41467-024-52334-1
ISSN:2041-1723
Establishing a robust triangulation framework to explore the relationship between hearing loss and Parkinson’s disease
Hao Zhang•Keying Chen•Tongyu Gao•Yu Yan•Ying Liu等 11 人
Npj Parkinson's Disease
2025
•2025/1/3
•Vol.11 No.1 p.1-12
The relationship between hearing loss (HL) and Parkinson’s disease (PD) remains unclear. Using individual-level and summary-level data from the UK Biobank and the largest genome-wide association studies, we examined this link through observational, Mendelian randomization and genetic pleiotropy anal...
Parkinson's diseaseRisk factors
10.1038/S41531-024-00861-5
ISSN:2373-8057
Genetic analyses implicate complex links between adult testosterone levels and health and disease
Leinonen Jaakko T.•Mars Nina•Lehtonen Leevi E.•Ahola-Olli Ari•Ruotsalainen Sanni等 14 人
Communications Medicine
2023
•2023/1/18
•Vol.3 No.1 p.1-15
Testosterone levels are linked with diverse characteristics of human health, yet, whether these associations reflect correlation or causation remains debated. Here, we provide a broad perspective on the role of genetically determined testosterone on complex diseases in both sexes. Leveraging genetic...
Endocrine system and metabolic diseasesGenome-wide association studiesMedical genomicsReproductive biology
10.1038/S43856-022-00226-0
ISSN:2730-664X
Genome-wide fine-mapping improves identification of causal variants
Yang Wu•Zhili Zheng•Loic Thibaut•Tian Lin•Qian Feng等 11 人
Nature Genetics
2026
•2026/3/30
•00 p.1-12
Fine-mapping refines genotype–phenotype association signals to identify causal variants underlying complex traits. However, current methods typically focus on individual genomic loci and do not account for the global genetic architecture. Here we demonstrate the advantages of performing genome-wide ...
Genetic association studyGenomics
10.1038/S41588-026-02549-3
ISSN:1061-4036
Discovery of core genes for systemic lupus erythematosus via genome-wide aggregated trans-effects analysis
Andrii Iakovliev•Olivia Castellini-Pérez•Buddhiprabha Erabadda•Javier Martín•Guillermo Barturen等 9 人
Genes & Immunity
2025
•2025/9/3
•00 p.1-12
The “omnigenic” hypothesis postulates that the polygenic effects of common variants on a typical complex trait coalesce on relatively few core genes through trans-effects on their expression. Our aim was to identify core genes for systemic lupus erythematosus (SLE) by testing for association with ge...
AutoimmunityChronic inflammationDisease geneticsGenome-wide association studies
10.1038/S41435-025-00352-4
ISSN:1476-5470
A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization
Jue-Sheng Ong•Suzanne C. Dixon-Suen•Xikun Han•Jiyuan An•Upekha Liyanage等 24 人
Nature Communications
2021
•2021/1/11
•Vol.12 No.1 p.1-10
Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associate...
Cancer epidemiologyCancer geneticsCancer prevention
10.1038/S41467-020-20368-W
ISSN:2041-1723
Cardiovascular measures from abdominal MRI provide insights into abdominal vessel genetic architecture
Nicolas Basty•Elena P. Sorokin•Marjola Thanaj•Brandon Whitcher•Yi Liu等 8 人
Communications Medicine
2026
•2026/2/2
•Vol.6 No.1 p.700
Cardiovascular disease remains a major source of morbidity and mortality, and population imaging studies have yielded insights into disease etiology and risk. In this study, we segment the heart, aorta, and vena cava from abdominal magnetic resonance imaging (MRI) scans using deep learning. We gener...
Cardiovascular diseasesCardiovascular geneticsComputational biology and bioinformatics
10.1038/S43856-025-01242-6
ISSN:2730-664X
Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration
Stefan Groeneweg•Ferdy S. van Geest•Mariano Martín•Mafalda Dias•Jonathan Frazer等 122 人
Nature Communications
2025
•2025/3/12
•Vol.16 No.1 p.1-21
Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for ‘actionable’ genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) variants cause a rare neurodevelo...
EndocrinologyGeneticsMachine learningNeurodevelopmental disorders
10.1038/S41467-025-56628-W
ISSN:2041-1723
Genetic basis of early onset and progression of type 2 diabetes in South Asians
Sam Hodgson•Alice Williamson•Margherita Bigossi•Daniel Stow•Benjamin M. Jacobs等 14 人
Nature Medicine
2024
•2024/11/26
•00 p.1-9
South Asians develop type 2 diabetes (T2D) early in life and often with normal body mass index (BMI). However, reasons for this are poorly understood because genetic research is largely focused on European ancestry groups. We used recently derived multi-ancestry partitioned polygenic scores (pPSs) t...
Disease geneticsGenetics researchType 2 diabetes
10.1038/S41591-024-03317-8
ISSN:1078-8956
Quantifying the impact of early life growth adversity on later life health
Raphael Goldman-Pham•Matthew P. Alter•Rebecca Bao•Sophie É. Collins•Catherine L. Debban等 33 人
Communications Medicine
2025
•2025/11/17
0Early-life growth adversity is important to later-life health, but precision assessment in adulthood is challenging. We evaluated whether the difference between attained and genotype-predicted adult height (“height-GaP”) would associate with prospectively ascertained early-life growth adversity and ...
AgeingCardiovascular diseasesEpidemiology
10.1038/S43856-025-01245-3
ISSN:2730-664X
Associations of body composition measures with circulating insulin-like growth factor-I, testosterone, and sex hormone-binding globulin concentrations in 16,000 men
Matthew C. Hynes•Cody Z. Watling•Yashvee Dunneram•Timothy J. Key•Aurora Perez-Cornago
International Journal Of Obesity
2024
•2024/10/21
•00 p.1-9
Adiposity is positively associated with risk of some cancer sites and other health conditions in men; however, it is unclear if endogenous hormones play a role in these associations. We examined how body composition, measured from magnetic resonance imaging (MRI) and common measures of adiposity (e....
ObesityRisk factors
10.1038/S41366-024-01633-0
ISSN:0307-0565
The brain structure, inflammatory, and genetic mechanisms mediate the association between physical frailty and depression
Rongtao Jiang•Stephanie Noble•Matthew Rosenblatt•Wei Dai•Jean Ye等 10 人
Nature Communications
2024
•2024/5/23
•Vol.15 No.1 p.1-11
Cross-sectional studies have demonstrated strong associations between physical frailty and depression. However, the evidence from prospective studies is limited. Here, we analyze data of 352,277 participants from UK Biobank with 12.25-year follow-up. Compared with non-frail individuals, pre-frail an...
DepressionNeural ageingPredictive markers
10.1038/S41467-024-48827-8
ISSN:2041-1723
Assessing single-cell transcriptomic variability through density-preserving data visualization
Ashwin Narayan•Bonnie Berger•Hyunghoon Cho
Nature Biotechnology
2021
•2021/1/18
•00 p.1-10
Nonlinear data visualization methods, such as t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP), summarize the complex transcriptomic landscape of single cells in two dimensions or three dimensions, but they neglect the local density of data...
Computational biology and bioinformaticsData miningTranscriptomics
10.1038/S41587-020-00801-7
ISSN:1087-0156
Accurate estimation of SNP-heritability from biobank-scale data irrespective of genetic architecture
Kangcheng Hou•Kathryn S. Burch•Arunabha Majumdar•Huwenbo Shi•Nicholas Mancuso等 8 人
Nature Genetics
2019
•2019/7/29
•Vol.51 No.8 p.1244-1251
SNP-heritability is a fundamental quantity in the study of complex traits. Recent studies have shown that existing methods to estimate genome-wide SNP-heritability can yield biases when their assumptions are violated. While various approaches have been proposed to account for frequency- and linkage ...
Genome-wide association studiesPopulation genetics
10.1038/S41588-019-0465-0
ISSN:1061-4036
Genetic legacy of ancient hunter-gatherer Jomon in Japanese populations
Kenichi Yamamoto•Shinichi Namba•Kyuto Sonehara•Ken Suzuki•Saori Sakaue等 19 人
Nature Communications
2024
•2024/11/12
•Vol.15 No.1 p.1-15
The tripartite ancestral structure is a recently proposed model for the genetic origin of modern Japanese, comprising indigenous Jomon hunter-gatherers and two additional continental ancestors from Northeast Asia and East Asia. To investigate the impact of the tripartite structure on genetic and phe...
Evolutionary biologyEvolutionary geneticsGenetic variationGenome informaticsRisk factors
10.1038/S41467-024-54052-0
ISSN:2041-1723
Large-scale cross-ancestry genome-wide meta-analysis of serum urate
Chamlee Cho•Beomsu Kim•Dan Say Kim•Mi Yeong Hwang•Injeong Shim等 17 人
Nature Communications
2024
•2024/4/24
•Vol.15 No.1 p.1-17
Hyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate requires exploration. A large-scale cross-ancest...
Genetics researchGenome-wide association studies
10.1038/S41467-024-47805-4
ISSN:2041-1723
RNA alternative splicing impacts the risk for alcohol use disorder
Rudong Li•Jill L. Reiter•Andy B. Chen•Steven X. Chen•Tatiana Foroud等 8 人
Molecular Psychiatry
2023
•2023/5/23
•00 p.1-12
Alcohol use disorder (AUD) is a complex genetic disorder characterized by problems arising from excessive alcohol consumption. Identifying functional genetic variations that contribute to risk for AUD is a major goal. Alternative splicing of RNA mediates the flow of genetic information from DNA to g...
GeneticsMolecular biology
10.1038/S41380-023-02111-1
ISSN:1359-4184
Characterization of cis-regulatory elements and functional variants in colorectal cancer using epigenomics and CRISPRi screenings
Zequn Lu•Can Chen•Heng Zhang•Bin Li•Yizhuo Liu等 37 人
Nature Cancer
2025
•2025/8/25
•00 p.1-23
Genetic variants associated with colorectal cancer (CRC) are primarily noncoding and reside in cis-regulatory elements (CREs), yet their underlying mechanisms remain elusive. Here we established a dynamic epigenetic atlas using multiomics data from 533 colorectal tissues spanning normal to advanced ...
CancerCancer genomicsColorectal cancerGenome-wide association studies
10.1038/S43018-025-01031-Z
ISSN:2662-1347
Cross-population GWAS and proteomics improve risk prediction and reveal mechanisms in atrial fibrillation
Shuai Yuan•Jie Chen•Xixin Ruan•Yuying Li•Sarah A. Abramowitz等 17 人
Nature Communications
2025
•2025/7/11
•Vol.16 No.1 p.1-13
Atrial fibrillation (AF) is a common cardiac arrhythmia with strong genetic components, yet its underlying molecular mechanisms and potential therapeutic targets remain incompletely understood. We conducted a cross-population genome-wide meta-analysis of 168,007 AF cases and identified 525 loci that...
Cardiovascular geneticsGenome-wide association studiesPredictive markersRisk factors
10.1038/S41467-025-61720-2
ISSN:2041-1723
MC3R links nutritional state to childhood growth and the timing of puberty
Lam B. Y. H.•Williamson A.•Finer S.•Day F. R.•Tadross J. A.等 40 人
Nature
2021
•2021/11/3
•00 p.1-6
The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2...
EndocrinologyQuantitative traitReproductive biology
10.1038/S41586-021-04088-9
ISSN:0028-0836
Prospective cohort study evaluating the association between influenza vaccination and neurodegenerative diseases
Houyu Zhao•Xuan Zhou•Kexin Fu•Yunxiao Duan•Qiaorui Wen等 7 人
Npj Vaccines
2024
•2024/3/2
•Vol.9 No.1 p.1-9
The effect of influenza vaccination (FluVac) on the risk of neurodegenerative diseases has not been well evaluated in prospective populations. We aimed to assess the association between FluVac and the risk of dementia and Parkinson’s disease (PD) in people aged 60 years or older through a prospectiv...
Alzheimer's diseaseEpidemiologyParkinson's disease
10.1038/S41541-024-00841-Z
ISSN:2059-0105
New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders
Evangelos Evangelou•He Gao•Congying Chu•Georgios Ntritsos•Paul Blakeley等 98 人
Nature Human Behaviour
2019
•2019/7/29
•Vol.3 No.9 p.950-961
Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d−1) from the UK Biobank, the Alcohol Genome-Wide Consortium and...
GeneticsRisk factors
10.1038/S41562-019-0653-Z
ISSN:2397-3374
Genome-wide meta-analysis identifies 93 risk loci and enables risk prediction equivalent to monogenic forms of venous thromboembolism
Ghouse Jonas•Tragante Vinicius•Ahlberg Gustav•Rand Søren A.•Jespersen Jakob B.等 36 人
Nature Genetics
2023
•2023/1/19
•Vol.55 No.3 p.399-409
We report a genome-wide association study of venous thromboembolism (VTE) incorporating 81,190 cases and 1,419,671 controls sampled from six cohorts. We identify 93 risk loci, of which 62 are previously unreported. Many of the identified risk loci are at genes encoding proteins with functions conver...
Genome-wide association studiesThromboembolism
10.1038/S41588-022-01286-7
ISSN:1061-4036
Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions
David M. Howard•Mark J. Adams•Toni-Kim Clarke•Jonathan D. Hafferty•Jude Gibson等 29 人
Nature Neuroscience
2019
•2019/2/4
•Vol.22 No.3 p.343-352
Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analy...
DepressionGenome-wide association studies
10.1038/S41593-018-0326-7
ISSN:1097-6256
Rare deleterious germline variants and risk of lung cancer
Yanhong Liu•Jun Xia•James McKay•Spiridon Tsavachidis•Xiangjun Xiao等 47 人
Npj Precision Oncology
2021
•2021/2/16
•Vol.5 No.1 p.1-12
Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal varian...
Cancer epidemiologyNon-small-cell lung cancer
10.1038/S41698-021-00146-7
ISSN:2397-768X
Association of fine particulate matter constituents with chronic obstructive pulmonary disease and the effect modification of genetic susceptibility
Meiqi Xing•Feipeng Cui•Lei Zheng•Yudiyang Ma•Jianing Wang等 10 人
Npj Climate And Atmospheric Science
2025
•2025/3/5
•Vol.8 No.1 p.1-9
This study investigated the link between long-term exposure to PM2.5 components and the risk of developing chronic obstructive pulmonary disease (COPD) using UK Biobank data. The exposure dataset, derived from the European Monitoring and Evaluation Program (EMEP) model, included elemental carbon (EC...
Atmospheric chemistryEnvironmental impact
10.1038/S41612-025-00967-4
ISSN:2397-3722
Efficient and accurate frailty model approach for genome-wide survival association analysis in large-scale biobanks
Dey Rounak•Zhou Wei•Kiiskinen Tuomo•Havulinna Aki•Elliott Amanda等 13 人
Nature Communications
2022
•2022/9/16
•Vol.13 No.1 p.1-13
With decades of electronic health records linked to genetic data, large biobanks provide unprecedented opportunities for systematically understanding the genetics of the natural history of complex diseases. Genome-wide survival association analysis can identify genetic variants associated with ages ...
Genome-wide association studiesRisk factorsStatistical methods
10.1038/S41467-022-32885-X
ISSN:2041-1723
Air pollutants, residential greenspace, and the risk of kidney stone disease: a large prospective cohort study from the UK Biobank
Minghui Liu•Meng Gao•Zewu Zhu•Jiao Hu•Jian Wu等 8 人
Journal Of Exposure Science & Environmental Epidemiology
2024
•2024/10/22
•00 p.1-9
The epidemiological evidence regarding the correlation between air pollution, residential greenspace, and the risk of kidney stone disease (KSD) is limited, with no large-scale prospective studies conducted on this relationship. We conducted a large-scale prospective study from the UK Biobank to exp...
Medicine/Public Health, generalEpidemiology
10.1038/S41370-024-00728-0
ISSN:1559-0631
A PheWAS approach to identify associations of GBA1 variants with comprehensive phenotypes beyond neurological diseases
Jiaqi Yang•Yuanfeng Huang•Zheng Wang•Shiyu Zhang•Dai Wu等 16 人
Npj Parkinson's Disease
2025
•2025/3/17
•Vol.11 No.1 p.1-10
Given the established association between numerous GBA1 variants and specific neurological diseases, we extended the exploration by a phenome-wide association study to assess the impact of GBA1 variants on a wider spectrum of health-related traits. We identified 41 phenotypes associated with GBA1 va...
Computational biology and bioinformaticsDiseasesGeneticsMedical researchNeurologyNeuroscience+2
10.1038/S41531-025-00901-8
ISSN:2373-8057
Association of birth and childhood weight with risk of chronic diseases and multimorbidity in adulthood
Yue Zhang•Yaguan Zhou•Yangyang Cheng•Rodrigo M. Carrillo-Larco•Muhammad Fawad等 7 人
Communications Medicine
2023
•2023/7/31
•Vol.3 No.1 p.1-9
Little is known about the relationship between early life body size and occurrence of life-course multiple chronic diseases (multimorbidity). We aim to evaluate associations of birth weight, childhood body size, and their changes with the risks of chronic diseases and multimorbidity. This prospectiv...
EpidemiologyPublic health
10.1038/S43856-023-00335-4
ISSN:2730-664X
Whole-exome imputation within UK Biobank powers rare coding variant association and fine-mapping analyses
Alison R. Barton•Maxwell A. Sherman•Ronen E. Mukamel•Po-Ru Loh
Nature Genetics
2021
•2021/7/5
•00 p.1-10
Exome association studies to date have generally been underpowered to systematically evaluate the phenotypic impact of very rare coding variants. We leveraged extensive haplotype sharing between 49,960 exome-sequenced UK Biobank participants and the remainder of the cohort (total n ≈ 500,000) to imp...
Genome-wide association studiesGenomics
10.1038/S41588-021-00892-1
ISSN:1061-4036
Genetic loci shared between major depression and intelligence with mixed directions of effect
Shahram Bahrami•Alexey Shadrin•Oleksandr Frei•Kevin S. O’Connell•Francesco Bettella等 15 人
Nature Human Behaviour
2021
•2021/1/18
•00 p.1-7
Genome-wide association studies (GWAS) have identified several common genetic variants influencing major depression and general cognitive abilities, but little is known about whether the two share any of their genetic aetiology. Here we investigate shared genomic architectures between major depressi...
Behavioural geneticsBioinformatics
10.1038/S41562-020-01031-2
ISSN:2397-3374
Collider bias undermines our understanding of COVID-19 disease risk and severity
Gareth J. Griffith•Tim T. Morris•Matthew J. Tudball•Annie Herbert•Giulia Mancano等 14 人
Nature Communications
2020
•2020/11/12
•Vol.11 No.1 p.1-12
Numerous observational studies have attempted to identify risk factors for infection with SARS-CoV-2 and COVID-19 disease outcomes. Studies have used datasets sampled from patients admitted to hospital, people tested for active infection, or people who volunteered to participate. Here, we highlight ...
EpidemiologyInfectious diseasesRisk factorsStatistical methods
10.1038/S41467-020-19478-2
ISSN:2041-1723
Partitioned polygenic scores show mechanistic heterogeneity in type 2 diabetes and hypertension comorbidity
Vincent Pascat•Liudmila Zudina•Lucas Maurin•Anna Ulrich•Jared G. Maina等 17 人
Nature Communications
2026
•2026/2/9
•Vol.17 No.1 p.14460
Type 2 diabetes and hypertension are common health conditions that often occur together, suggesting shared biological mechanisms. To explore this relationship, we analyse large-scale multiomic data to uncover genetic factors underlying type 2 diabetes and blood pressure comorbidity. We curate 1304 i...
Genetic predisposition to diseaseHypertensionPersonalized medicineType 2 diabetes
10.1038/S41467-025-67449-2
ISSN:2041-1723
Patterns of brain asymmetry associated with polygenic risks for autism and schizophrenia implicate language and executive functions but not brain masculinization
Zhiqiang Sha•Dick Schijven•Clyde Francks
Molecular Psychiatry
2021
•2021/7/1
•00 p.1-9
Autism spectrum disorder (ASD) and schizophrenia have been conceived as partly opposing disorders in terms of systemizing vs. empathizing cognitive styles, with resemblances to male vs. female average sex differences. Left–right asymmetry of the brain is an important aspect of its organization that ...
Autism spectrum disordersGeneticsNeuroscienceSchizophrenia
10.1038/S41380-021-01204-Z
ISSN:1359-4184
ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon
Sylvia Hartmann•Summaira Yasmeen•Benjamin M. Jacobs•Spiros Denaxas•Munir Pirmohamed等 10 人
Nature Communications
2023
•2023/10/12
•Vol.14 No.1 p.1-11
Raynaud’s phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses fro...
Genetics researchRheumatologyTranslational research
10.1038/S41467-023-41876-5
ISSN:2041-1723
Cost-effectiveness of CA125- and age-informed risk-based triage for ovarian cancer detection in primary care
Runguo Wu•Kirsten D. Arendse•Tooba Hamdani•Fiona M. Walter•Emma J. Crosbie等 7 人
British Journal Of Cancer
2025
•2025/9/17
•00 p.1-9
In England, current practice is cancer antigen 125 (CA125) testing with pelvic ultrasound scan (USS) if CA125 is ≥35 U/mL for triage of women with suspected ovarian cancer (OC) in primary care. However, OC risk varies with CA125 level and age. The Ovatools model predicts OC risk based on age and CA1...
Health care economicsOvarian cancerPredictive markers
10.1038/S41416-025-03166-3
ISSN:0007-0920
Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
Fernandez-Rozadilla Ceres•Timofeeva Maria•Chen Zhishan•Law Philip•Thomas Minta等 210 人
Nature Genetics
2022
•2022/12/20
•Vol.55 No.1 p.89-99
Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integr...
Colorectal cancerEpigenomicsGenome-wide association studiesTranscriptomics
10.1038/S41588-022-01222-9
ISSN:1061-4036
Neuroanatomical dimensions in major depression linked to cognition, adverse life events, self-harm, metabolomics and genetics
Wenyi Xiao•Rachel D. Woodham•Yuhan Cui•Junhao Wen•Mathilde Antoniades等 50 人
Communications Medicine
2025
•2025/11/15
0Major depressive disorder (MDD) is a leading cause of disability worldwide, yet its diagnosis relies on clinical symptoms alone. Using the semi-supervised machine learning algorithm, Heterogeneity through Discriminative Analysis (HYDRA), we had identified two neuroanatomical dimensions in deeply phe...
BiomarkersBrainDepression
10.1038/S43856-025-01219-5
ISSN:2730-664X
Scalable and accurate rare variant meta-analysis with Meta-SAIGE
Eunjae Park•Kisung Nam•Seokho Jeong•Karl Keat•Dokyoon Kim等 8 人
Nature Genetics
2025
•2025/11/20
•00 p.1-8
Meta-analysis enhances the power of rare variant association tests by combining summary statistics across several cohorts. However, existing methods often fail to control type I error for low-prevalence binary traits and are computationally intensive. Here we introduce Meta-SAIGE—a scalable method f...
BioinformaticsGenetics researchGenome-wide association studiesSoftware
10.1038/S41588-025-02403-Y
ISSN:1061-4036
Correcting for volunteer bias in GWAS increases SNP effect sizes and heritability estimates
Sjoerd van Alten•Benjamin W. Domingue•Jessica Faul•Titus Galama•Andries T. Marees
Nature Communications
2025
•2025/4/15
•Vol.16 No.1 p.1-11
Selection bias in genome-wide association studies (GWASs) due to volunteer-based sampling (volunteer bias) is poorly understood. The UK Biobank (UKB), one of the largest and most widely used cohorts, is highly selected. Using inverse probability (IP) weights we estimate inverse probability weighted ...
Behavioural geneticsGenome-wide association studiesStatistics
10.1038/S41467-025-58684-8
ISSN:2041-1723
Causal effects on complex traits are similar for common variants across segments of different continental ancestries within admixed individuals
Hou Kangcheng•Ding Yi•Xu Ziqi•Wu Yue•Bhattacharya Arjun等 29 人
Nature Genetics
2023
•2023/3/20
•00 p.1-10
Individuals of admixed ancestries (for example, African Americans) inherit a mosaic of ancestry segments (local ancestry) originating from multiple continental ancestral populations. This offers the unique opportunity of investigating the similarity of genetic effects on traits across ancestries wit...
Computational biology and bioinformaticsGenome-wide association studiesPopulation genetics
10.1038/S41588-023-01338-6
ISSN:1061-4036
Disease clusters and their genetic determinants following a diagnosis of depression: analyses based on a novel three-dimensional disease network approach
Can Hou•Haowen Liu•Yu Zeng•Yike Gong•Huazhen Yang等 9 人
Molecular Psychiatry
2025
•2025/7/18
•00 p.1-11
Depression is strongly associated with a range of subsequent diseases. To elucidate key mechanistic pathways for targeted interventions, this study aimed to determine the main disease networks associated with depression as well as their underlying genetic determinants. We developed a novel three-dim...
DepressionGenetics
10.1038/S41380-025-03120-Y
ISSN:1359-4184
Associations between trajectories of plasma biomarkers for Alzheimer’s disease, brain structures, and cognitive function: a prospective cohort study in the UK Biobank
Xin Huang•Xiaolei Han•Hongli Chang•Tianyu Yu•Yi Dong等 17 人
Molecular Psychiatry
2025
•2025/8/28
•00 p.1-12
Plasma amyloid-β(Aβ)42/40 ratio, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and phosphorylated tau181(p-tau181) are promising biomarkers for Alzheimer’s disease (AD)-related pathology. We aimed to explore the longitudinal trajectories of these biomarkers in association with c...
NeurosciencePredictive markersPrognostic markers
10.1038/S41380-025-03166-Y
ISSN:1359-4184
Artificial intelligence-driven metabolomics of retinal nerve fibre layer to profile risks of mortality and cardiometabolic diseases
Shaopeng Yang•Zhuoyao Xin•Huangdong Li•Ziyu Zhu•Lisa Zhuoting Zhu等 14 人
Nature Communications
2025
•2025/12/11
•Vol.16 No.1 p.110390
Retinal nerve fibre layer (RNFL) is a non-invasive structural biomarker of cardiometabolic health, yet its biological underpinnings remain unknown. Here, we integrate advanced retinal optical biopsy and artificial intelligence (AI) algorithms with two complementary metabolomic assays across eth...
EpidemiologyEye manifestationsPredictive markersPreventive medicineRisk factors
10.1038/S41467-025-66979-Z
ISSN:2041-1723
The mitigation effects of residential green space and low air pollution on socioeconomic inequalities in depression
Qi Wu•Chenshuang Li•Luxia Zhang•Ying Zhou
Npj Mental Health Research
2025
•2025/8/1
•Vol.4 No.1 p.1-9
Depression is highly clustered among people with low socioeconomic status (SES). Improved environments are known to be potentially beneficial, but the extent to which environments alleviate socioeconomic inequalities in depression remains unclear. Based on 334,536 UK Biobank participants, we quantif...
DepressionEnvironmental impact
10.1038/S44184-025-00152-8
ISSN:2731-4251
Low depression frequency is associated with decreased risk of cardiometabolic disease
Honigberg Michael C.•Ye Yixuan•Dattilo Lillian•Sarma Amy A.•Scott Nandita S.等 9 人
Nature Cardiovascular Research
2022
•2022/2/14
•00 p.1-7
Polygenic risk scores (PRS) are an increasingly available tool to refine risk prediction for cardiometabolic diseases1. Favorable lifestyle behaviors might offset increased polygenic risk, but whether frequency of depressed mood stratifies PRS-associated risk is unknown. Here, we calculated individu...
CardiologyCardiovascular diseasesPopulation geneticsType 2 diabetes
10.1038/S44161-021-00011-7
ISSN:2731-0590
The role of circadian rest-activity rhythm for the link between 25-hydroxyvitamin D and type 2 diabetes: a cohort study
Hanzhang Wu•Hongliang Feng•Jiahe Wei•Shuai Wang•Liangkai Chen等 8 人
Nutrition & Diabetes
2025
•2025/10/23
•Vol.15 No.1 p.1-11
Temporal distribution and amplitude of physical activity/inactivity in 24 h known as circadian rest-activity rhythm may predict the risk of various metabolic diseases, including type 2 diabetes (T2D), yet the mechanisms behind the diurnal behavior patterns remain largely unexplored. This study inclu...
Risk factorsType 2 diabetes
10.1038/S41387-025-00395-6
ISSN:2044-4052
Effects of diets on risks of cancer and the mediating role of metabolites
Yi Fan•Chanchan Hu•Xiaoxu Xie•Yanfeng Weng•Chen Chen等 11 人
Nature Communications
2024
•2024/7/13
•Vol.15 No.1 p.1-13
Research on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using the UK Biobank data, we prospectively investigate the associations between adherence to a Mediterranean diet (MedDiet) or a Mediterranean...
Cancer epidemiologyEpidemiologyMolecular medicine
10.1038/S41467-024-50258-4
ISSN:2041-1723
Brain–heart–eye axis revealed by multi-organ imaging genetics and proteomics
Aleix Boquet-Pujadas•Filippos Anagnostakis•Michael R. Duggan•Cassandra M. Joynes•Arthur W. Toga等 9 人
Nature Biomedical Engineering
2025
•2025/9/30
•00 p.1-23
Multi-organ research investigates interconnections among multiple human organ systems, enhancing our understanding of human aging and disease mechanisms. Here we use multi-organ imaging, individual- and summary-level genetics, and proteomics data consolidated via the MULTI Consortium to delineate a ...
Genetics researchHeritable quantitative traitMachine learning
10.1038/S41551-025-01506-5
ISSN:2157-846X
The genetic architecture of human amygdala volumes and their overlap with common brain disorders
Ou Ya-Nan•Wu Bang-Sheng•Ge Yi-Jun•Zhang Yi•Jiang Yu-Chao等 11 人
Translational Psychiatry
2023
•2023/3/11
•Vol.13 No.1 p.1-12
The amygdala is a crucial interconnecting structure in the brain that performs several regulatory functions, yet its genetic architectures and involvement in brain disorders remain largely unknown. We carried out the first multivariate genome-wide association study (GWAS) of amygdala subfield volume...
DiseasesNeuroscience
10.1038/S41398-023-02387-5
ISSN:2158-3188
Whole exome sequencing identified six novel genes for depressive symptoms
Ze-Yu Li•Chen-Jie Fei•Rui-Ying Yin•Ju-Jiao Kang•Qing Ma等 16 人
Molecular Psychiatry
2024
•2024/10/29
•00 p.1-12
Previous genome-wide association studies of depression have primarily focused on common variants, limiting our comprehensive understanding of the genetic architecture. In contrast, whole–exome sequencing can capture rare coding variants, helping to explore the phenotypic consequences of altering pro...
DepressionGenetics
10.1038/S41380-024-02804-1
ISSN:1359-4184
A quantitative trait locus for reduced microglial APOE expression associates with reduced cerebral amyloid angiopathy
Michael E. Belloy•Jonathan Graff-Radford•Michael D. Greicius
Nature Genetics
2026
•2026/1/26
•Vol.58 No.2 p.271-272
Alzheimer's diseaseGene regulationGenetic association study
10.1038/S41588-025-02472-Z
ISSN:1061-4036
Multimodal population study reveals the neurobiological underpinnings of chronotype
Le Zhou•Karin Saltoun•Julie Carrier•Kai-Florian Storch•Robin I. M. Dunbar等 6 人
Nature Human Behaviour
2025
•2025/4/17
•00 p.1-15
The rapid shifts in society have altered human behavioural patterns, with increased evening activities, increased screen time and changed sleep schedules. As an explicit manifestation of circadian rhythms, chronotype is closely intertwined with physical and mental health. Night owls often exhibit un...
Human behaviourSleep
10.1038/S41562-025-02182-W
ISSN:2397-3374
Multivariate genomic analysis of 5 million people elucidates the genetic architecture of shared components of the metabolic syndrome
Sanghyeon Park•Soyeon Kim•Beomsu Kim•Dan Say Kim•Jaeyoung Kim等 22 人
Nature Genetics
2024
•2024/9/30
•00 p.1-12
Metabolic syndrome (MetS) is a complex hereditary condition comprising various metabolic traits as risk factors. Although the genetics of individual MetS components have been investigated actively through large-scale genome-wide association studies, the conjoint genetic architecture has not been ful...
Genome-wide association studiesMetabolic disordersPopulation genetics
10.1038/S41588-024-01933-1
ISSN:1061-4036
Haplotype-based inference of recent effective population size in modern and ancient DNA samples
Romain Fournier•Zoi Tsangalidou•David Reich•Pier Francesco Palamara
Nature Communications
2023
•2023/12/1
•Vol.14 No.1 p.1-13
Individuals sharing recent ancestors are likely to co-inherit large identical-by-descent (IBD) genomic regions. The distribution of these IBD segments in a population may be used to reconstruct past demographic events such as effective population size variation, but accurate IBD detection is difficu...
Conservation biologyPopulation geneticsStatistical methods
10.1038/S41467-023-43522-6
ISSN:2041-1723
DeepNull models non-linear covariate effects to improve phenotypic prediction and association power
McCaw Zachary R.•Colthurst Thomas•Yun Taedong•Furlotte Nicholas A.•Carroll Andrew等 8 人
Nature Communications
2022
•2022/1/11
•Vol.13 No.1 p.1-10
Genome-wide association studies (GWASs) examine the association between genotype and phenotype while adjusting for a set of covariates. Although the covariates may have non-linear or interactive effects, due to the challenge of specifying the model, GWAS often neglect such terms. Here we introduce D...
Genetic association studyGenetics research
10.1038/S41467-021-27930-0
ISSN:2041-1723
Exome-wide analysis implicates rare protein-altering variants in human handedness
Dick Schijven•Sourena Soheili-Nezhad•Simon E. Fisher•Clyde Francks
Nature Communications
2024
•2024/4/2
•Vol.15 No.1 p.1-12
Handedness is a manifestation of brain hemispheric specialization. Left-handedness occurs at increased rates in neurodevelopmental disorders. Genome-wide association studies have identified common genetic effects on handedness or brain asymmetry, which mostly involve variants outside protein-coding ...
Behavioural geneticsHuman behaviourRare variants
10.1038/S41467-024-46277-W
ISSN:2041-1723
Sex differences in the genetic regulation of the human plasma proteome
Mine Koprulu•Eleanor Wheeler•Nicola D. Kerrison•Spiros Denaxas•Julia Carrasco-Zanini等 10 人
Nature Communications
2025
•2025/5/13
•Vol.16 No.1 p.1-10
Mechanisms underlying sex differences in the development and prognosis of many diseases remain largely elusive. Here, we systematically investigated sex differences in the genetic regulation of plasma proteome (>5800 protein targets) across two cohorts (30,307 females; 26,058 males). Plasma level...
GenomicsProteomics
10.1038/S41467-025-59034-4
ISSN:2041-1723
Whole exome sequencing analysis identifies genes for alcohol consumption
Jujiao Kang•Yue-Ting Deng•Bang-Sheng Wu•Wei-Shi Liu•Ze-Yu Li等 13 人
Nature Communications
2024
•2024/7/10
•Vol.15 No.1 p.1-15
Alcohol consumption is a heritable behavior seriously endangers human health. However, genetic studies on alcohol consumption primarily focuses on common variants, while insights from rare coding variants are lacking. Here we leverage whole exome sequencing data across 304,119 white British individu...
Behavioural geneticsGenetic association studyHealth care
10.1038/S41467-024-50132-3
ISSN:2041-1723
Retinal morphology across the menstrual cycle: insights from the UK Biobank
Ana Paula Ribeiro Reis•Estelle Ioannidou•Siegfried Karl Wagner•Robbert Struyven•Zihan Sun等 15 人
Npj Women's Health
2024
•2024/11/8
•Vol.2 No.1 p.1-12
Oestradiol and progesterone levels are higher in menstruating women than men of the same age, and their receptors are present in their neurosensory retina and retinal pigment epithelium. However, the impact of this hormonal environment on retinal physiology in women remains unclear. Using self-repor...
DiagnosisHealth care
10.1038/S44294-024-00042-Y
ISSN:2948-1716
Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression
Jamie E. Craig•Xikun Han•Ayub Qassim•Mark Hassall•Jessica N. Cooke Bailey等 44 人
Nature Genetics
2020
•2020/1/20
•Vol.52 No.2 p.160-166
Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic ri...
Genetic association studyGenetics researchTranslational research
10.1038/S41588-019-0556-Y
ISSN:1061-4036
Evaluating the informativeness of deep learning annotations for human complex diseases
Kushal K. Dey•Bryce van de Geijn•Samuel Sungil Kim•Farhad Hormozdiari•David R. Kelley等 6 人
Nature Communications
2020
•2020/9/17
•Vol.11 No.1 p.1-9
Deep learning models have shown great promise in predicting regulatory effects from DNA sequence, but their informativeness for human complex diseases is not fully understood. Here, we evaluate genome-wide SNP annotations from two previous deep learning models, DeepSEA and Basenji, by applying strat...
Autoimmune diseasesMachine learningMutagenesis
10.1038/S41467-020-18515-4
ISSN:2041-1723
Machine learning reveals distinct neuroanatomical signatures of cardiovascular and metabolic diseases in cognitively unimpaired individuals
Sindhuja Tirumalai Govindarajan•Elizabeth Mamourian•Guray Erus•Ahmed Abdulkadir•Randa Melhem等 29 人
Nature Communications
2025
•2025/3/19
•Vol.16 No.1 p.1-12
Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic resonance imaging signatures (MRI) remain poorly characterized. To address this, we developed and validated machine learning models to quantify the d...
DementiaDiagnostic markersMachine learningNeuroscienceRisk factors
10.1038/S41467-025-57867-7
ISSN:2041-1723
Associations of abdominal obesity and plasma fatty acids with microvascular diseases
Ruidie Shi•Lan Yu•Shengnan Liu•Guangbin Sun•Dongfang Zhang等 10 人
Communications Medicine
2026
•2026/1/3
•Vol.6 No.1 p.730
The independent and interactive associations of abdominal obesity and fatty acids with the risk of microvascular diseases (MVDs) are still unclear. We conducted a prospective cohort study of 88,571 participants aged 40-69 years from the UK Biobank. Plasma fatty acids were quantified at baseline usin...
Cardiovascular diseasesEpidemiology
10.1038/S43856-025-01333-4
ISSN:2730-664X
Leveraging functional genomic annotations and genome coverage to improve polygenic prediction of complex traits within and between ancestries
Zhili Zheng•Shouye Liu•Julia Sidorenko•Ying Wang•Tian Lin等 16 人
Nature Genetics
2024
•2024/4/30
•00 p.1-11
We develop a method, SBayesRC, that integrates genome-wide association study (GWAS) summary statistics with functional genomic annotations to improve polygenic prediction of complex traits. Our method is scalable to whole-genome variant analysis and refines signals from functional annotations by all...
Genome-wide association studiesGenomics
10.1038/S41588-024-01704-Y
ISSN:1061-4036
No causal links between estradiol and female’s brain and mental health using Mendelian randomization
Hannah Oppenheimer•Dennis van der Meer•Louise S. Schindler•Arielle Crestol•Alexey Shadrin等 9 人
Nature Communications
2025
•2025/12/5
•Vol.16 No.1 p.109150
The role of estradiol in depression and Alzheimer’s disease – brain disorders that disproportionately affect females – is debated. Results from observational studies are inconsistent and limited by confounding and reverse causation. To overcome these limitations, we perform two-sample Mendelian rand...
Alzheimer's diseaseComputational neuroscienceDepressionGenetics researchPsychology
10.1038/S41467-025-65878-7
ISSN:2041-1723
Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis
Jonas Ghouse•Gardar Sveinbjörnsson•Marijana Vujkovic•Anne-Sofie Seidelin•Helene Gellert-Kristensen等 51 人
Nature Genetics
2024
•2024/4/17
•00 p.1-11
We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver func...
Genome-wide association studiesLiver cirrhosis
10.1038/S41588-024-01720-Y
ISSN:1061-4036
Physical activity levels may impact on the risk of premature mortality in people with epilepsy
Lingjie Fan•Shengyi Liu•Junhan Zhao•Xiyue Wang•Yanyi Nie等 16 人
Nature Communications
2025
•2025/11/7
•Vol.16 No.1 p.1-14
Epilepsy affects over 70 million individuals worldwide, with optimal physical activity (PA) levels remaining challenging to determine due to potential negative outcomes from both insufficient and excessive activity. To quantify the associations between objective PA and mortality in people with epile...
EpidemiologyEpilepsyHealth care
10.1038/S41467-025-64805-0
ISSN:2041-1723
Endophenotype effect sizes support variant pathogenicity in monogenic disease susceptibility genes
Halford Jennifer L.•Morrill Valerie N.•Choi Seung Hoan•Jurgens Sean J.•Melloni Giorgio等 44 人
Nature Communications
2022
•2022/8/30
•Vol.13 No.1 p.1-11
Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotei...
CardiologyCardiovascular diseasesGenetic testingMolecular medicine
10.1038/S41467-022-32009-5
ISSN:2041-1723
Rapid and accurate multi-phenotype imputation for millions of individuals
Lin-Lin Gu•Hong-Shan Wu•Tian-Yi Liu•Yong-Jie Zhang•Jing-Cheng He等 10 人
Nature Communications
2025
•2025/1/4
•Vol.16 No.1 p.1-13
Deep phenotyping can enhance the power of genetic analysis, including genome-wide association studies (GWAS), but the occurrence of missing phenotypes compromises the potential of such resources. Although many phenotypic imputation methods have been developed, the accurate imputation of millions of ...
BioinformaticsGenetic association studyMachine learning
10.1038/S41467-024-55496-0
ISSN:2041-1723
Cerebral small vessel disease genomics and its implications across the lifespan
Muralidharan Sargurupremraj•Hideaki Suzuki•Xueqiu Jian•Chloé Sarnowski•Tavia E. Evans等 116 人
Nature Communications
2020
•2020/12/8
•Vol.11 No.1 p.1-18
White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding b...
Genome-wide association studiesWhite matter disease
10.1038/S41467-020-19111-2
ISSN:2041-1723
Sleep disturbances as risk factors for neurodegeneration later in life
Emily Simmonds•Kristin S. Levine•Jun Han•Hirotaka Iwaki•Mathew J. Koretsky等 16 人
Npj Dementia
2025
•2025/5/27
•Vol.1 No.1 p.1-10
The relationship between sleep disorders and neurodegeneration is complex. Using >1 million electronic health records from Wales, UK, and Finland, we mined biobank data to identify relationships between sleep disorders and neurodegenerative diseases (NDDs). Additionally, we investigated how sleep...
Circadian rhythms and sleepEpidemiologyLifestyle modificationNeurological disorders
10.1038/S44400-025-00008-0
ISSN:3005-1940
Distinct genetic liability profiles define clinically relevant patient strata across common diseases
Lucia Trastulla•Georgii Dolgalev•Sylvain Moser•Laura T. Jiménez-Barrón•Till F. M. Andlauer等 20 人
Nature Communications
2024
•2024/7/1
•Vol.15 No.1 p.1-28
Stratified medicine holds great promise to tailor treatment to the needs of individual patients. While genetics holds great potential to aid patient stratification, it remains a major challenge to operationalize complex genetic risk factor profiles to deconstruct clinical heterogeneity. Contemp...
Functional clusteringGenetics researchGenome-wide association studiesMedical genomics
10.1038/S41467-024-49338-2
ISSN:2041-1723
Multiparameter prediction of myeloid neoplasia risk
Muxin Gu•Sruthi Cheloor Kovilakam•William G. Dunn•Ludovica Marando•Clea Barcena等 14 人
Nature Genetics
2023
•2023/8/24
•00 p.1-8
The myeloid neoplasms encompass acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms. Most cases arise from the shared ancestor of clonal hematopoiesis (CH). Here we analyze data from 454,340 UK Biobank participants, of whom 1,808 developed a myeloid neoplasm 0–15 years...
Genetics researchHaematological cancerOutcomes research
10.1038/S41588-023-01472-1
ISSN:1061-4036
Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height
Gareth Hawkes•Robin N. Beaumont•Zilin Li•Ravi Mandla•Xihao Li等 57 人
Nature Communications
2024
•2024/10/3
•Vol.15 No.1 p.1-11
The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003),...
Gene regulationGenome-wide association studiesQuantitative trait
10.1038/S41467-024-52579-W
ISSN:2041-1723
Accurate and efficient estimation of local heritability using summary statistics and the linkage disequilibrium matrix
Hui Li•Rahul Mazumder•Xihong Lin
Nature Communications
2023
•2023/12/2
•Vol.14 No.1 p.1-13
Existing SNP-heritability estimators that leverage summary statistics from genome-wide association studies (GWAS) are much less efficient (i.e., have larger standard errors) than the restricted maximum likelihood (REML) estimators which require access to individual-level data. We introduce a new met...
Computational biology and bioinformaticsGenome-wide association studies
10.1038/S41467-023-43565-9
ISSN:2041-1723
Metabolic fingerprinting on retinal pigment epithelium thickness for individualized risk stratification of type 2 diabetes mellitus
Shaopeng Yang•Zhuoting Zhu•Shida Chen•Yixiong Yuan•Mingguang He等 6 人
Nature Communications
2023
•2023/10/18
•Vol.14 No.1 p.1-12
The retina is an important target organ of diabetes mellitus, with increasing evidence from patients and animal models suggesting that retinal pigment epithelium (RPE) may serve as an early marker for diabetes-related damages. However, their longitudinal relationship and the biological underpinnings...
Population screeningPredictive markersType 2 diabetes
10.1038/S41467-023-42404-1
ISSN:2041-1723
Genetic association of inflammatory marker GlycA with lung function and respiratory diseases
Yanjun Guo•Quanhong Liu•Zhilin Zheng•Mengxia Qing•Tianci Yao等 12 人
Nature Communications
2024
•2024/5/4
•Vol.15 No.1 p.1-10
Association of circulating glycoprotein acetyls (GlycA), a systemic inflammation biomarker, with lung function and respiratory diseases remain to be investigated. We examined the genetic correlation, shared genetics, and potential causality of GlycA (N = 115,078) with lung function and respiratory d...
EpidemiologyGenetic association studyRespiratory tract diseases
10.1038/S41467-024-47845-W
ISSN:2041-1723
Genome-wide association study and polygenic risk prediction of hypothyroidism
Søren A. Rand•Gustav Ahlberg•Vinicius Tragante•Laia M. Monfort•Chaoqun Zheng等 30 人
Nature Genetics
2025
•2025/11/14
•00 p.1-9
We performed a genome-wide meta-analysis of hypothyroidism (113,393 cases and 1,065,268 controls), free thyroxine (191,449 individuals) and thyroid-stimulating hormone (482,873 individuals). We identified 350 loci associated with hypothyroidism, including 179 not previously reported, 29 of which wer...
Genome-wide association studiesThyroid diseases
10.1038/S41588-025-02410-Z
ISSN:1061-4036
Association of accelerometer-derived circadian abnormalities and genetic risk with incidence of atrial fibrillation
Yang Lulu•Feng Hongliang•Ai Sizhi•Liu Yue•Lei Binbin等 12 人
Npj Digital Medicine
2023
•2023/3/4
•Vol.6 No.1 p.1-8
Evidence suggests potential links between circadian rhythm and atrial fibrillation (AF). However, whether circadian disruption can predict the onset of AF in the general population remains largely unknown. We aim to investigate the association of accelerometer-measured circadian rest-activity rhythm...
Atrial fibrillationRisk factors
10.1038/S41746-023-00781-3
ISSN:2398-6352
Molecular and micro-architectural mapping of gray matter alterations in psychosis
Natalia García-San-Martín•Richard A. I. Bethlehem•Agoston Mihalik•Jakob Seidlitz•Isaac Sebenius等 21 人
Molecular Psychiatry
2024
•2024/9/12
•00 p.1-10
The psychosis spectrum encompasses a heterogeneous range of clinical conditions associated with abnormal brain development. Detecting patterns of atypical neuroanatomical maturation across psychiatric disorders requires an interpretable metric standardized by age-, sex- and site-effect. The molecula...
NeuroscienceSchizophrenia
10.1038/S41380-024-02724-0
ISSN:1359-4184
Photoreceptor metabolic window unveils eye–body interactions
Shaopeng Yang•Zhuoyao Xin•Weijing Cheng•Pingting Zhong•Riqian Liu等 12 人
Nature Communications
2025
•2025/1/15
•Vol.16 No.1 p.1-16
Photoreceptors are specialized neurons at the core of the retina’s functionality, with optical accessibility and exceptional sensitivity to systemic metabolic stresses. Here we show the ability of risk-free, in vivo photoreceptor assessment as a window into systemic health and identify shared metabo...
EpidemiologyPrognostic markersRisk factorsTranslational research
10.1038/S41467-024-55035-X
ISSN:2041-1723
Multicenter proteome-wide Mendelian randomization study identifies causal plasma proteins in melanoma and non-melanoma skin cancers
Yajia Li•Qiangxiang Li•Ziqin Cao•Jianhuang Wu
Communications Biology
2024
•2024/7/13
•Vol.7 No.1 p.1-13
This study addresses the diagnostic and therapeutic challenges in malignant melanoma (MM) and non-melanoma skin cancers (NMSC). We aim to identify circulating proteins causally linked to MM and NMSC traits using a multicenter Mendelian randomization (MR) framework. We utilized large-scale cis-MR to ...
Diagnostic markersMelanoma
10.1038/S42003-024-06538-2
ISSN:2399-3642
Pre-diagnostic clonal hematopoiesis of indeterminate potential among patients with a primary cancer and risk of second cancers
Xinyuan Liu•Hans-Olov Adami•Erik Boberg•Karin E. Smedby•Hui Wei等 7 人
Leukemia
2026
•2026/4/14
•00 p.1-7
Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an elevated risk of hematologic and solid cancers. We performed a prospective cohort study, including 63690 patients with a first diagnosis of primary cancer in the UK Biobank during 2006 to 2022, to investigate the associatio...
Cancer epidemiologyEpidemiology
10.1038/S41375-026-02946-X
ISSN:0887-6924
Genetics implicates overactive osteogenesis in the development of diffuse idiopathic skeletal hyperostosis
Anurag Sethi•J. Graham Ruby•Matthew A. Veras•Natalie Telis•Eugene Melamud
Nature Communications
2023
•2023/5/8
•Vol.14 No.1 p.1-14
Diffuse idiopathic skeletal hyperostosis (DISH) is a condition where adjacent vertebrae become fused through formation of osteophytes. The genetic and epidemiological etiology of this condition is not well understood. Here, we implemented a machine learning algorithm to assess the prevalence and sev...
EpidemiologyGenome-wide association studiesMedical genetics
10.1038/S41467-023-38279-X
ISSN:2041-1723
Predicted leukocyte telomere length and risk of germ cell tumours
Cigan Shannon S.•Meredith John J.•Kelley Ava C.•Yang Tianzhong•Langer Erica K.等 12 人
British Journal Of Cancer
2022
•2022/4/2
•00 p.1-12
Genetically predicted leukocyte telomere length (LTL) has been evaluated in several studies of childhood and adult cancer. We test whether genetically predicted longer LTL is associated with germ cell tumours (GCT) in children and adults. Paediatric GCT samples were obtained from a Children’s Oncolo...
Cancer geneticsGerm cell tumoursPaediatric cancer
10.1038/S41416-022-01798-3
ISSN:0007-0920
Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors
Nicole M. Warrington•Robin N. Beaumont•Momoko Horikoshi•Felix R. Day•Øyvind Helgeland等 73 人
Nature Genetics
2019
•2019/5/1
•Vol.51 No.5 p.804-814
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mother...
GeneticsGenome-wide association studies
10.1038/S41588-019-0403-1
ISSN:1061-4036
Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions
Mark P. Purdue•Diptavo Dutta•Mitchell J. Machiela•Bryan R. Gorman•Timothy Winter等 132 人
Nature Genetics
2024
•2024/4/26
•00 p.1-10
Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell...
Genome-wide association studiesRenal cell carcinoma
10.1038/S41588-024-01725-7
ISSN:1061-4036
Unraveling the link between CNVs, cognition and individual neuroimaging deviation scores from a population-based reference cohort
Charlotte Fraza•Ida E. Sønderby•Rune Boen•Yingjie Shi•Christian F. Beckmann等 6 人
Nature Mental Health
2024
•2024/11/1
•00 p.1-13
Copy number variations (CNVs) are genetic variants that can have a substantial influence on neurodevelopment, neuropsychiatric traits and morphometric brain changes, yet their impact at the individual level remains unknown. Common case–control approaches for analyzing CNVs suffer from limitations; t...
NeuroscienceRisk factors
10.1038/S44220-024-00322-1
ISSN:2731-6076
Polygenic overlap between subjective well-being and psychiatric disorders and cross-ancestry validation
Jin Young Jung•Yeeun Ahn•Jung-Wook Park•Kyeongmin Jung•Soyeon Kim等 17 人
Nature Human Behaviour
2025
•2025/4/14
•00 p.1-11
Subjective well-being (SWB) is important for understanding human behaviour and health. Although the connection between SWB and psychiatric disorders has been studied, common genetic mechanisms remain unclear. This study aimed to explore the genetic relationship between SWB and psychiatric disorders....
Genetics researchMedical genetics
10.1038/S41562-025-02155-Z
ISSN:2397-3374
Long-term obesity impacts brain morphology, functional connectivity and cognition in adults
Die Zhang•Chenye Shen•Nanguang Chen•Chaoqiang Liu•Jun Hu等 8 人
Nature Mental Health
2025
•2025/3/3
•00 p.1-13
Although obesity has been implicated in brain and cognitive health, the effect of longitudinal obesity trajectories on brain and cognitive aging remains insufficiently understood. Here, using multifaceted obesity measurements from the UK Biobank, we identified five distinct obesity trajectories: low...
Neural ageingPredictive markers
10.1038/S44220-025-00396-5
ISSN:2731-6076
LDAK-KVIK performs fast and powerful mixed-model association analysis of quantitative and binary phenotypes
Jasper P. Hof•Doug Speed
Nature Genetics
2025
•2025/8/11
•00 p.1-8
Mixed-model association analysis (MMAA) is the preferred tool for performing genome-wide association studies. However, existing MMAA tools often have long runtimes and high memory requirements. Here we present LDAK-KVIK, an MMAA tool for analysis of quantitative and binary phenotypes. LDAK-KVIK is c...
Genome-wide association studiesSoftware
10.1038/S41588-025-02286-Z
ISSN:1061-4036
Enhancing mitochondrial one-carbon metabolism is neuroprotective in Alzheimer’s disease models
Yizhou Yu•Civia Z. Chen•Ivana Celardo•Bryan Wei Zhi Tan•James D. Hurcomb等 9 人
Cell Death & Disease
2024
•2024/11/24
•Vol.15 No.11 p.1-16
Alzheimer’s disease (AD) is the most common form of age-related dementia. In AD, the death of neurons in the central nervous system is associated with the accumulation of toxic amyloid β peptide (Aβ) and mitochondrial dysfunction. Mitochondria are signal transducers of metabolic and biochemical info...
Alzheimer's diseaseEnergy metabolism
10.1038/S41419-024-07179-3
ISSN:2041-4889
Proteomic signatures of sweetened beverages are associated with higher risk of adverse liver outcomes
Longgang Zhao•Xinyuan Zhang•Jiali Zheng•Yun Chen•Danielle E. Haslam等 11 人
Nature Food
2025
•2025/12/1
•Vol.6 No.12 p.1186-1195
Evidence is limited on the associations between the consumption of sweetened beverages, their proteomic signatures and liver health. We used data from the UK Biobank with 173,840 participants aged 40–69 years and applied Cox proportional hazards regression to examine associations of sugar- and artif...
EpidemiologyNon-alcoholic fatty liver diseaseNutritionRisk factors
10.1038/S43016-025-01266-0
ISSN:2662-1355
Biological aging predicts mortality in Parkinson’s patients: evidence from UK Biobank
Qing-Qing Duan•Wei-Ming Su•Kang-Fu Yin•Sheng-Yi He•Ru-Yin Liu等 10 人
Npj Parkinson's Disease
2026
•2026/1/21
•Vol.12 No.1 p.530
Accelerated biological aging serves as a risk factor for age-related diseases, its role in the prognosis of PD remains ambiguous. This study investigates the association between biological aging and the mortality in PD patients. Data were sourced from the UK Biobank. Independent prognostic factors f...
BiomarkersDiseasesMedical researchNeurologyRisk factors
10.1038/S41531-026-01268-0
ISSN:2373-8057
Accurate, scalable and integrative haplotype estimation
Olivier Delaneau•Jean-François Zagury•Matthew R. Robinson•Jonathan L. Marchini•Emmanouil T. Dermitzakis
Nature Communications
2019
•2019/11/28
•Vol.10 No.1 p.1-10
The number of human genomes being genotyped or sequenced increases exponentially and efficient haplotype estimation methods able to handle this amount of data are now required. Here we present a method, SHAPEIT4, which substantially improves upon other methods to process large genotype and high cove...
Computational modelsDNA sequencingHaplotypesSoftware
10.1038/S41467-019-13225-Y
ISSN:2041-1723
Genome-wide association study of serum liver enzymes implicates diverse metabolic and liver pathology
Vincent L. Chen•Xiaomeng Du•Yanhua Chen•Annapurna Kuppa•Samuel K. Handelman等 11 人
Nature Communications
2021
•2021/2/5
•Vol.12 No.1 p.1-13
Serum liver enzyme concentrations are the most frequently-used laboratory markers of liver disease, a major cause of mortality. We conduct a meta-analysis of genome-wide association studies of liver enzymes from UK BioBank and BioBank Japan. We identified 160 previously-unreported independent alanin...
BiomarkersGenome-wide association studiesLiver diseases
10.1038/S41467-020-20870-1
ISSN:2041-1723
Pervasive interactions between exposures and polygenic risk can inform more effective clinical and behavioral interventions
Sini Nagpal•Greg Gibson
Nature Genetics
2026
•2026/7/13
•00 p.1-10
The generalizability of polygenic scores (PGS) remains a major hurdle in the pursuit of equitable genomic medicine. Differences in disease prevalence across groups, potentially including social strata, influence the relationship between PGS and risk. Here we quantified the magnitude of PGS-by-contex...
Genome-wide association studiesMetabolic disorders
10.1038/S41588-026-02674-Z
ISSN:1061-4036
Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data
Wainschtein Pierrick•Jain Deepti•Zheng Zhili•Cupples L. Adrienne•Shadyab Aladdin H.等 50 人
Nature Genetics
2022
•2022/3/7
•Vol.54 No.3 p.263-273
Analyses of data from genome-wide association studies on unrelated individuals have shown that, for human traits and diseases, approximately one-third to two-thirds of heritability is captured by common SNPs. However, it is not known whether the remaining heritability is due to the imperfect tagging...
Genetic association studyPopulation genetics
10.1038/S41588-021-00997-7
ISSN:1061-4036
Associations of biological ageing and genetic risk with incident abdominal aortic aneurysm
Chen Yao•Guochang You•Runnan Shen•Kangjie Wang•Yunhao Sun等 7 人
Communications Medicine
2026
•2026/1/9
•Vol.6 No.1 p.1070
Abdominal aortic aneurysm (AAA) is a degenerative cardiovascular disorder prevalent with ageing. While accelerated biological ageing contributes to age-related diseases, its specific role in AAA risk remains unclear. This study investigates the relationships between biological ageing and risk of inc...
AneurysmPredictive markers
10.1038/S43856-025-01373-W
ISSN:2730-664X
AI-driven preclinical disease risk assessment using imaging in UK biobank
Dmitrii Seletkov•Sophie Starck•Tamara T. Mueller•Yundi Zhang•Lisa Steinhelfer等 7 人
Npj Digital Medicine
2025
•2025/7/26
•Vol.8 No.1 p.1-8
Identifying disease risk and detecting disease before clinical symptoms appear are essential for early intervention and improving patient outcomes. In this context, the integration of medical imaging in a clinical workflow offers a unique advantage by capturing detailed structural and functional inf...
DiseasesRisk factors
10.1038/S41746-025-01771-3
ISSN:2398-6352
Genetically proxied HTRA1 protease activity and circulating levels independently predict risk of ischemic stroke and coronary artery disease
Rainer Malik•Nathalie Beaufort•Jiang Li•Koki Tanaka•Marios K. Georgakis等 13 人
Nature Cardiovascular Research
2024
•2024/5/20
•00 p.1-13
Genetic variants in HTRA1 are associated with stroke risk. However, the mechanisms mediating this remain largely unknown, as does the full spectrum of phenotypes associated with genetic variation in HTRA1. Here we show that rare HTRA1 variants are linked to ischemic stroke in the UK Biobank and BioB...
Genetics researchMyocardial infarctionStroke
10.1038/S44161-024-00475-3
ISSN:2731-0590
Translating polygenic risk scores for clinical use by estimating the confidence bounds of risk prediction
Sun Jiangming•Wang Yunpeng•Folkersen Lasse•Borné Yan•Amlien Inge等 13 人
Nature Communications
2021
•2021/9/6
•Vol.12 No.1 p.1-9
A promise of genomics in precision medicine is to provide individualized genetic risk predictions. Polygenic risk scores (PRS), computed by aggregating effects from many genomic variants, have been developed as a useful tool in complex disease research. However, the application of PRS as a tool for ...
Machine learningPopulation geneticsPredictive markers
10.1038/S41467-021-25014-7
ISSN:2041-1723
Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy
Krzysztof Kiryluk•Elena Sanchez-Rodriguez•Xu-Jie Zhou•Francesca Zanoni•Lili Liu等 188 人
Nature Genetics
2023
•2023/6/19
•00 p.1-15
IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. Here we performed a genome-wide association study of 10,146 kidney-biopsy-diagnosed IgAN cases and 28,751 controls across 17 international cohorts. We defined 30 genome-wide significant risk loci ...
Genome-wide association studiesIgA nephropathy
10.1038/S41588-023-01422-X
ISSN:1061-4036
Unravelling the complex causal effects of substance use behaviours on common diseases
Angli Xue•Zhihong Zhu•Huanwei Wang•Longda Jiang•Peter M. Visscher等 7 人
Communications Medicine
2024
•2024/3/12
•Vol.4 No.1 p.1-13
Substance use behaviours (SUB) including smoking, alcohol consumption, and coffee intake are associated with many health outcomes. However, whether the health effects of SUB are causal remains controversial, especially for alcohol consumption and coffee intake. In this study, we assess 11 commonly u...
EpidemiologyGenetic variationGenome-wide association studies
10.1038/S43856-024-00473-3
ISSN:2730-664X
Fast and flexible joint fine-mapping of multiple traits via the Sum of Single Effects model
Yuxin Zou•Peter Carbonetto•Dongyue Xie•Gao Wang•Matthew Stephens
Nature Genetics
2026
•2026/2/3
•Vol.58 No.2 p.454-462
We introduce mvSuSiE, a multitrait fine-mapping method, to identify putative causal variants from genetic association data (individual-level or summary). mvSuSiE learns patterns of shared genetic effects from data, and exploits these patterns to improve power to identify causal single nucleotide pol...
Genome-wide association studiesSoftware
10.1038/S41588-025-02486-7
ISSN:1061-4036
Proteome-wide mendelian randomization identifies causal plasma proteins in venous thromboembolism development
Haobo Li•Zhu Zhang•Yuting Qiu•Haoyi Weng•Shuai Yuan等 16 人
Journal Of Human Genetics
2023
•2023/8/3
•00 p.1-8
Genome-wide association studies (GWAS) have identified numerous risk loci for venous thromboembolism (VTE), but it is challenging to decipher the underlying mechanisms. We employed an integrative analytical pipeline to transform genetic associations to identify novel plasma proteins for VTE. Proteom...
Genome-wide association studiesThromboembolism
10.1038/S10038-023-01186-6
ISSN:1434-5161
Genetic basis of right and left ventricular heart shape
Richard Burns•William J. Young•Nay Aung•Luis R. Lopes•Perry M. Elliott等 12 人
Nature Communications
2024
•2024/11/14
•Vol.15 No.1 p.1-17
Heart shape captures variation in cardiac structure beyond traditional phenotypes of mass and volume. Although observational studies have demonstrated associations with cardiometabolic risk factors and diseases, its genetic basis is less understood. We utilised cardiovascular magnetic resonance imag...
Cardiovascular biologyGenetic association study
10.1038/S41467-024-53594-7
ISSN:2041-1723
Genome-wide interaction association analysis identifies interactive effects of childhood maltreatment and kynurenine pathway on depression
Yaoyao Sun•Yundan Liao•Yuyanan Zhang•Zhe Lu•Yuzhuo Ma等 18 人
Nature Communications
2025
•2025/2/18
•Vol.16 No.1 p.1-12
Childhood maltreatment stands out as a pivotal risk factor for depression, with gene-by-environment interaction serving as a crucial mechanism. Here we perform genome-wide interaction analyzes of childhood maltreatment in the UK Biobank, integrating methylation evidence through colocalization analys...
DepressionGenetic interactionHuman behaviour
10.1038/S41467-025-57066-4
ISSN:2041-1723
Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease
Chengyi Ding•Linda Ng Fat•Annie Britton•Pek Kei Im•Kuang Lin等 11 人
Nature Communications
2023
•2023/12/14
•Vol.14 No.1 p.1-8
Alcohol-related liver disease (ARLD) represents a major public health burden. Identification of high-risk individuals would allow efficient targeting of public health interventions. Here, we show significant interactions between pattern of drinking, genetic predisposition (polygenic risk score, PRS)...
Alcoholic liver diseaseEpidemiologyGenome-wide association studies
10.1038/S41467-023-43064-X
ISSN:2041-1723
Phenotypic effects of genetic variants associated with autism
Thomas Rolland•Freddy Cliquet•Richard J. L. Anney•Clara Moreau•Nicolas Traut等 25 人
Nature Medicine
2023
•2023/6/26
•00 p.1-10
While over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in individuals without a diagnosis of autism. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Based on data from more than 13,000 individuals...
Autism spectrum disordersGenetics research
10.1038/S41591-023-02408-2
ISSN:1078-8956
X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements
Markus Scholz•Katrin Horn•Janne Pott•Matthias Wuttke•Andreas Kühnapfel等 159 人
Nature Communications
2024
•2024/1/18
•Vol.15 No.1 p.1-17
X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide si...
Genetic association studyKidney diseases
10.1038/S41467-024-44709-1
ISSN:2041-1723
Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms
Jing Guo•Klaudia Walter•Pedro M. Quiros•Muxin Gu•E. Joanna Baxter等 16 人
Nature Genetics
2024
•2024/1/17
•00 p.1-8
Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example, JAK2V617F, are common in the population, yet only a minority of carriers develop MPN. Here we show that the inherited polygenic loci that und...
DNA sequencingPopulation genetics
10.1038/S41588-023-01638-X
ISSN:1061-4036
Exploiting family history in aggregation unit-based genetic association tests
Wang Yanbing•Chen Han•Peloso Gina M.•DeStefano Anita L.•Dupuis Josée
European Journal Of Human Genetics
2021
•2021/10/25
•00 p.1-8
The development of sequencing technology calls for new powerful methods to detect disease associations and lower the cost of sequencing studies. Family history (FH) contains information on disease status of relatives, adding valuable information about the probands’ health problems and risk of diseas...
Genetic association studyGenetics research
10.1038/S41431-021-00980-0
ISSN:1018-4813
Poor sleep and shift work associate with increased blood pressure and inflammation in UK Biobank participants
Monica Kanki•Artika P. Nath•Ruidong Xiang•Stephanie Yiallourou•Peter J. Fuller等 8 人
Nature Communications
2023
•2023/11/4
•Vol.14 No.1 p.1-15
Disrupted circadian rhythms have been linked to an increased risk of hypertension and cardiovascular disease. However, many studies show inconsistent findings and are not sufficiently powered for targeted subgroup analyses. Using the UK Biobank cohort, we evaluate the association between circadian r...
Endocrine system and metabolic diseasesGenetic databasesHypertension
10.1038/S41467-023-42758-6
ISSN:2041-1723
Large language models improve transferability of electronic health record-based predictions across countries and coding systems
Matthias Kirchler•Matteo Ferro•Veronica Lorenzini•Robin P. van de Water•Christoph Lippert等 6 人
Npj Digital Medicine
2026
•2026/1/22
•Vol.9 No.1 p.1770
Variation in medical practices and reporting standards across healthcare systems limits the transferability of prediction models based on structured electronic health record data. Prior studies have demonstrated that embedding medical codes into a shared semantic space can help address these discrep...
Medical researchRisk factors
10.1038/S41746-026-02363-5
ISSN:2398-6352
Multivariate analysis reveals shared genetic architecture of brain morphology and human behavior
de Vlaming Ronald•Slob Eric A. W.•Jansen Philip R.•Dagher Alain•Koellinger Philipp D.等 7 人
Communications Biology
2021
•2021/10/12
•Vol.4 No.1 p.1-9
Human variation in brain morphology and behavior are related and highly heritable. Yet, it is largely unknown to what extent specific features of brain morphology and behavior are genetically related. Here, we introduce a computationally efficient approach for multivariate genomic-relatedness-based ...
Behavioural geneticsPopulation genetics
10.1038/S42003-021-02712-Y
ISSN:2399-3642
Mediating and moderating effects of plasma proteomic biomarkers on the association between poor oral health problems and brain white matter microstructural integrity: the UK Biobank study
May A. Beydoun•Hind A. Beydoun•Yi-Han Hu•Zhiguang Li•Michael F. Georgescu等 11 人
Molecular Psychiatry
2024
•2024/7/30
•00 p.1-14
The plasma proteome can mediate associations between periodontal disease (Pd) and brain white matter integrity (WMI). We screened 5089 UK Biobank participants aged 40–70 years for poor oral health problems (POHP). We examined the association between POHP and WMI (fractional anisotropy (FA), mean dif...
Biological techniquesMolecular biologyNeurosciencePredictive markers
10.1038/S41380-024-02678-3
ISSN:1359-4184
Genetic associations of protein-coding variants in venous thromboembolism
Xiao-Yu He•Bang-Sheng Wu•Liu Yang•Yu Guo•Yue-Ting Deng等 14 人
Nature Communications
2024
•2024/4/1
•Vol.15 No.1 p.1-12
Previous genetic studies of venous thromboembolism (VTE) have been largely limited to common variants, leaving the genetic determinants relatively incomplete. We performed an exome-wide association study of VTE among 14,723 cases and 334,315 controls. Fourteen known and four novel genes (SRSF6, PHPT...
Genetic association studyThromboembolism
10.1038/S41467-024-47178-8
ISSN:2041-1723
Obesity-related biomarkers underlie a shared genetic architecture between childhood body mass index and childhood asthma
Han Xikun•Zhu Zhaozhong•Xiao Qian•Li Jun•Hong Xiumei等 9 人
Communications Biology
2022
•2022/10/17
•Vol.5 No.1 p.1-10
Obesity and asthma are both common diseases with high population burden worldwide. Recent genetic association studies have shown that obesity is associated with asthma in adults. The relationship between childhood obesity and childhood asthma, and the underlying mechanisms linking obesity to asthma ...
AsthmaGenome-wide association studies
10.1038/S42003-022-04070-9
ISSN:2399-3642
Sparse haplotype-based fine-scale local ancestry inference at scale reveals recent selection on immune responses
Yaoling Yang•Richard Durbin•Astrid K. N. Iversen•Daniel J. Lawson
Nature Communications
2025
•2025/3/20
•Vol.16 No.1 p.1-17
Increasingly efficient methods for inferring the ancestral origin of genome regions are needed to gain insights into genetic function and history as biobanks grow in scale. Here we describe two near-linear time algorithms to learn ancestry harnessing the strengths of a Positional Burrows-Wheeler Tra...
ImmunologyPopulation geneticsSoftware
10.1038/S41467-025-57601-3
ISSN:2041-1723
Genetic variants associated with longitudinal changes in brain structure across the lifespan
Brouwer Rachel M.•Klein Marieke•Grasby Katrina L.•Schnack Hugo G.•Jahanshad Neda等 200 人
Nature Neuroscience
2022
•2022/4/5
•00 p.1-12
Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, t...
Genetics of the nervous systemGenome-wide association studies
10.1038/S41593-022-01042-4
ISSN:1097-6256
Modified dementia risk score as a tool for the prediction of dementia: a prospective cohort study of 239745 participants
Wang Zuo-Teng•Fu Yan•Zhang Ya-Ru•Chen Shi-Dong•Huang Shu-Yi等 14 人
Translational Psychiatry
2022
•2022/12/10
•Vol.12 No.1 p.1-8
Based on risk profiles, several approaches for predicting dementia risk have been developed. Predicting the risk of dementia with accuracy is a significant clinical challenge. The goal was to create a modified dementia risk score (MDRS) based on a big sample size. A total of 239,745 participants fro...
DiseasesNeuroscience
10.1038/S41398-022-02269-2
ISSN:2158-3188
Measured and genetically predicted protein levels and cardiovascular diseases in UK Biobank and China Kadoorie Biobank
Lars Lind•Mohsen Mazidi•Robert Clarke•Derrick A. Bennett•Rui Zheng
Nature Cardiovascular Research
2024
•2024/9/25
•00 p.1-10
Several large-scale studies have measured plasma levels of the proteome in individuals with cardiovascular diseases (CVDs)1–7. However, since the majority of such proteins are interrelated2, it is difficult for observational studies to distinguish which proteins are likely to be of etiological relev...
Heart failureMyocardial infarctionProteomicsStrokeTranslational research
10.1038/S44161-024-00545-6
ISSN:2731-0590
An integrated germline and somatic genomic model for coronary artery disease
Xiong Yang•Min Seo Kim•Xinyu Zhu•Md Mesbah Uddin•Tetsushi Nakao等 52 人
Nature Communications
2026
•2026/3/26
0Multiple germline and somatic genomic factors are associated with risk of coronary artery disease, but there is no single measure of risk that integrates all information from a DNA sample. To address this gap, we develop an integrated genomic model that includes six germline and somatic genetic driv...
Cardiovascular geneticsComputational modelsGenetic predisposition to disease
10.1038/S41467-026-70379-2
ISSN:2041-1723
The genetic architecture of structural left–right asymmetry of the human brain
Zhiqiang Sha•Dick Schijven•Amaia Carrion-Castillo•Marc Joliot•Bernard Mazoyer等 8 人
Nature Human Behaviour
2021
•2021/3/15
•00 p.1-14
Left–right hemispheric asymmetry is an important aspect of healthy brain organization for many functions including language, and it can be altered in cognitive and psychiatric disorders. No mechanism has yet been identified for establishing the human brain’s left–right axis. We performed multivariat...
Behavioural geneticsGenetics of the nervous systemGenome-wide association studiesMagnetic resonance imagingPsychiatric disorders
10.1038/S41562-021-01069-W
ISSN:2397-3374
Common human genetic variants of APOE impact murine COVID-19 mortality
Ostendorf Benjamin N.•Patel Mira A.•Bilanovic Jana•Hoffmann H.-Heinrich•Carrasco Sebastian E.等 7 人
Nature
2022
•2022/9/21
•Vol.611 No.7935 p.346-351
Clinical outcomes of severe acute respiratory syndrome 2 (SARS-CoV-2) infection are highly heterogeneous, ranging from asymptomatic infection to lethal coronavirus disease 2019 (COVID-19). The factors underlying this heterogeneity remain insufficiently understood. Genetic association studies have su...
ImmunogeneticsInfectious diseases
10.1038/S41586-022-05344-2
ISSN:0028-0836
Genetic basis of falling risk susceptibility in the UK Biobank Study
Katerina Trajanoska•Lotta J. Seppala•Carolina Medina-Gomez•Yi-Hsiang Hsu•Sirui Zhou等 15 人
Communications Biology
2020
•2020/9/30
•Vol.3 No.1 p.1-10
Both extrinsic and intrinsic factors predispose older people to fall. We performed a genome-wide association analysis to investigate how much of an individual’s fall susceptibility can be attributed to genetics in 89,076 cases and 362,103 controls from the UK Biobank Study. The analysis revealed a s...
Genetic association studyRisk factors
10.1038/S42003-020-01256-X
ISSN:2399-3642
Wearable movement-tracking data identify Parkinson’s disease years before clinical diagnosis
Ann-Kathrin Schalkamp•Kathryn J. Peall•Neil A. Harrison•Cynthia Sandor
Nature Medicine
2023
•2023/7/3
•00 p.1-9
Parkinson’s disease is a progressive neurodegenerative movement disorder with a long latent phase and currently no disease-modifying treatments. Reliable predictive biomarkers that could transform efforts to develop neuroprotective treatments remain to be identified. Using UK Biobank, we investigate...
Diagnostic markersParkinson's diseasePopulation screeningPredictive medicine
10.1038/S41591-023-02440-2
ISSN:1078-8956
Using UK Biobank data to establish population-specific atlases from whole body MRI
Sophie Starck•Vasiliki Sideri-Lampretsa•Jessica J. M. Ritter•Veronika A. Zimmer•Rickmer Braren等 7 人
Communications Medicine
2024
•2024/11/19
•Vol.4 No.1 p.1-10
Reliable reference data in medical imaging is largely unavailable. Developing tools that allow for the comparison of individual patient data to reference data has a high potential to improve diagnostic imaging. Population atlases are a commonly used tool in medical imaging to facilitate this. Constr...
Population screeningWhole body imaging
10.1038/S43856-024-00670-0
ISSN:2730-664X
Endothelial TRIM47 regulates blood-brain barrier integrity and cognition via the KEAP1/NRF2 signalling pathway in mice
Valentin Delobel•Camille Grenier•Romain Boulestreau•Sébastien Rubin•Juliette Vaurs等 18 人
Communications Biology
2026
•2026/2/10
•Vol.9 No.1 p.3990
Cerebral small vessel disease (cSVD) is a leading cause of stroke, cognitive decline and dementia, for which no specific mechanism-based treatments are currently available. Previous genomic studies identified associations of common variants at chr17q25 with cSVD features, with converging evidence fo...
Blood–brain barrierCerebrovascular disordersDementiaVascular diseases
10.1038/S42003-026-09628-5
ISSN:2399-3642
Tractor uses local ancestry to enable the inclusion of admixed individuals in GWAS and to boost power
Elizabeth G. Atkinson•Adam X. Maihofer•Masahiro Kanai•Alicia R. Martin•Konrad J. Karczewski等 14 人
Nature Genetics
2021
•2021/1/18
•Vol.53 No.2 p.195-204
Admixed populations are routinely excluded from genomic studies due to concerns over population structure. Here, we present a statistical framework and software package, Tractor, to facilitate the inclusion of admixed individuals in association studies by leveraging local ancestry. We test Tractor w...
Computational biology and bioinformaticsGenetics researchGenome-wide association studiesGenomicsPopulation genetics
10.1038/S41588-020-00766-Y
ISSN:1061-4036
Refining the generation, interpretation and application of multi-organ, multi-omics biological aging clocks
Junhao Wen
Nature Aging
2025
•2025/8/5
•00 p.1-17
Multi-organ biological aging clocks derived from clinical phenotypes and neuroimaging data have emerged as valuable tools for studying human aging and disease. Plasma proteomics provides an additional molecular dimension to enrich these clocks. In this study, I developed 11 multi-organ proteome-base...
AgeingComputational modelsGenome-wide association studiesPredictive markers
10.1038/S43587-025-00928-9
ISSN:2662-8465
Observational and genetic evidence disagree on the association between loneliness and risk of multiple diseases
Yannis Yan Liang•Mingqing Zhou•Yu He•Weijie Zhang•Qiqi Wu等 11 人
Nature Human Behaviour
2024
•2024/9/16
•00 p.1-13
Loneliness—the subjective experience of social disconnection—is now widely regarded as a health risk factor. However, whether the associations between loneliness and multiple diseases are consistent with causal effects remains largely unexplored. Here we combined behavioural, genetic and hospitaliza...
DiseasesRisk factors
10.1038/S41562-024-01970-0
ISSN:2397-3374
C-reactive protein and residual cardiovascular risk in hypertension: a prospective cohort study
Anping Cai•Junguo Zhang•Stephen A. Clarkson•Gregory Y. H. Lip•Aletta E. Schutte等 8 人
Journal Of Human Hypertension
2026
•2026/3/11
•Vol.40 No.4 p.301-310
Control of systolic blood pressure (SBP) is important to prevent major adverse cardiovascular events (MACE) in hypertension. However, many individuals with controlled SBP still experience MACE, and the mechanisms remain relatively unknown. We sought to investigate whether elevated C-reactive protein...
HypertensionRisk factors
10.1038/S41371-026-01118-9
ISSN:1476-5527
Association of accelerometer-monitored physical activity with incident cataract: epidemiological and genetic evidence
Chenxiao Shen•Jiahui Cao•Zijing Du•Xianqi Zheng•Chunran Lai等 11 人
Eye
2026
•2026/7/23
•00 p.1-10
To investigate the association and potential causal relationship between accelerometer-assessed physical activity (PA) and the risk of senile cataract (SC). The study population was derived from the UK Biobank database. Triaxial accelerometer data from wearable devices, collected over a continuous 7...
Disease geneticsLens diseasesRisk factors
10.1038/S41433-026-04727-3
ISSN:0950-222X
Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells
Erik L. Bao•Satish K. Nandakumar•Xiaotian Liao•Alexander G. Bick•Juha Karjalainen等 25 人
Nature
2020
•2020/10/14
•Vol.586 No.7831 p.769-775
Myeloproliferative neoplasms (MPNs) are blood cancers that are characterized by the excessive production of mature myeloid cells and arise from the acquisition of somatic driver mutations in haematopoietic stem cells (HSCs). Epidemiological studies indicate a substantial heritable component of MPNs ...
Acute myeloid leukaemiaGenome-wide association studiesHaematopoiesisMyeloproliferative disease
10.1038/S41586-020-2786-7
ISSN:0028-0836
White matter micro- and macrostructure brain charts for the human lifespan
Michael E. Kim•Chenyu Gao•Karthik Ramadass•Nancy R. Newlin•Praitayini Kanakaraj等 30 人
Nature
2026
•2026/5/13
•00 p.1-11
The human brain relies on a complex network of connections to function, with white matter acting as the primary communication highway between different brain regions1,2. Disruptions in these critical communication pathways are linked to several neurological, psychiatric and developmental disorders3,...
Brain imagingData processing
10.1038/S41586-026-10454-2
ISSN:0028-0836
Meta-matching as a simple framework to translate phenotypic predictive models from big to small data
He Tong•An Lijun•Chen Pansheng•Chen Jianzhong•Feng Jiashi等 9 人
Nature Neuroscience
2022
•2022/5/16
•00 p.1-10
We propose a simple framework—meta-matching—to translate predictive models from large-scale datasets to new unseen non-brain-imaging phenotypes in small-scale studies. The key consideration is that a unique phenotype from a boutique study likely correlates with (but is not the same as) related pheno...
Cognitive neuroscienceNetwork models
10.1038/S41593-022-01059-9
ISSN:1097-6256
A plasma proteomics-based candidate biomarker panel predictive of amyotrophic lateral sclerosis
Ruth Chia•Ruin Moaddel•Justin Y. Kwan•Memoona Rasheed•Paola Ruffo等 40 人
Nature Medicine
2025
•2025/8/19
•00 p.1-11
Identifying a reliable biomarker for amyotrophic lateral sclerosis (ALS) is crucial for clinical practice. Here, in this cross-sectional study, we used the Olink Explore 3072 platform to investigate plasma proteomics as a biomarker tool for this neurodegenerative condition. Thirty-three proteins wer...
Diagnostic markersPredictive markers
10.1038/S41591-025-03890-6
ISSN:1078-8956
Plasma proteomic signatures of social isolation and loneliness associated with morbidity and mortality
Chun Shen•Ruohan Zhang•Jintai Yu•Barbara J. Sahakian•Wei Cheng等 6 人
Nature Human Behaviour
2025
•2025/1/3
•00 p.1-15
The biology underlying the connection between social relationships and health is largely unknown. Here, leveraging data from 42,062 participants across 2,920 plasma proteins in the UK Biobank, we characterized the proteomic signatures of social isolation and loneliness through proteome-wide associat...
Human behaviourProteomicsRisk factors
10.1038/S41562-024-02078-1
ISSN:2397-3374
Whole-genome sequencing analysis identifies rare, large-effect noncoding variants and regulatory regions associated with circulating protein levels
Gareth Hawkes•Kartik Chundru•Leigh Jackson•Kashyap A. Patel•Anna Murray等 10 人
Nature Genetics
2025
•2025/2/24
•Vol.57 No.3 p.626-634
The contribution of rare noncoding genetic variation to common phenotypes is largely unknown, as a result of a historical lack of population-scale whole-genome sequencing data and the difficulty of categorizing noncoding variants into functionally similar groups. To begin addressing these challenges...
Gene expressionGene regulationGenome-wide association studies
10.1038/S41588-025-02095-4
ISSN:1061-4036
DINGO: increasing the power of locus discovery in maternal and fetal genome-wide association studies of perinatal traits
Liang-Dar Hwang•Gabriel Cuellar-Partida•Loic Yengo•Jian Zeng•Jarkko Toivonen等 11 人
Nature Communications
2024
•2024/10/26
•Vol.15 No.1 p.1-14
Perinatal traits are influenced by fetal and maternal genomes. We investigate the performance of three strategies to detect loci in maternal and fetal genome-wide association studies (GWASs) of the same quantitative trait: (i) the traditional strategy of analysing maternal and fetal GWASs separately...
Quantitative traitQuantitative trait loci
10.1038/S41467-024-53495-9
ISSN:2041-1723
Identifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes
Monti Remo•Rautenstrauch Pia•Ghanbari Mahsa•James Alva Rani•Kirchler Matthias等 8 人
Nature Communications
2022
•2022/9/10
•Vol.13 No.1 p.1-16
Here we present an exome-wide rare genetic variant association study for 30 blood biomarkers in 191,971 individuals in the UK Biobank. We compare gene-based association tests for separate functional variant categories to increase interpretability and identify 193 significant gene-biomarker associati...
Diagnostic markersGenome-wide association studiesSequence annotation
10.1038/S41467-022-32864-2
ISSN:2041-1723
Sulfur microbial diet, genetical predisposition, and the risk of chronic kidney disease: a cohort study
Honghao Yang•Yixiao Zhang•Zheng Ma•Liuxin Li•Gang Zheng等 9 人
European Journal Of Clinical Nutrition
2026
•2026/2/16
•00 p.1-7
Our study evaluated the prospective association between the sulfur microbial diet (SMD), a diet associated with sulfur-metabolizing bacteria in stool, and the chronic kidney disease (CKD) risk, and further investigated whether genetic risk modified this association. This study involved 98,491 UK Bio...
DiseasesRisk factors
10.1038/S41430-026-01710-9
ISSN:0954-3007
Age-related changes in adiposity and cardiometabolic disease risk: a longitudinal and prospective study in the UK Biobank
Mathias Rask-Andersen•Valeria Lo Faro•Torgny Karlsson•Åsa Johansson
International Journal Of Obesity
2026
•2026/7/15
•00 p.1-10
Body mass index (BMI) is widely used to assess obesity-related disease risk but does not capture important aspects of fat distribution and ectopic fat deposition. Here we assess age-related differences in magnetic resonance imaging (MRI)-derived body composition measures and their relevance for card...
Medical researchRisk factors
10.1038/S41366-026-02168-2
ISSN:0307-0565
AI-based multiomics profiling reveals complementary omics contributions to personalized prediction of cardiovascular disease
Yan Luo•Nan Zhang•Jiannan Yang•Mengyao Cui•Kelvin K. F. Tsoi等 8 人
Nature Communications
2026
•2026/2/2
•Vol.17 No.1 p.22690
Genomics, metabolomics, and proteomics offer complementary insights into cardiovascular disease (CVD) risk. Leveraging UK Biobank data, we introduce the CardiOmicScore, a multitask deep learning framework, to learn disease-specific proteomic (ProScore) and metabolomic (MetScore) risk scores for the ...
Cardiovascular diseasesMachine learningPredictive markers
10.1038/S41467-026-68956-6
ISSN:2041-1723
Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves prediction across ancestry groups
Thomas J. Hoffmann•Rebecca E. Graff•Ravi K. Madduri•Alex A. Rodriguez•Clinton L. Cario等 49 人
Nature Genetics
2025
•2025/2/10
•Vol.57 No.2 p.334-344
We conducted a multiancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry, 58,236 African ancestry, 23,546 Hispanic/Latino and 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 in...
CancerGenome-wide association studies
10.1038/S41588-024-02068-Z
ISSN:1061-4036
Psychotropic medication use, lifestyle, genetic risk for high BMI and the incidence of cardiovascular disease
Nini de Boer•Iris Hanskamp•Bochao Danae Lin•Liese Boonstra•Marte van der Horst等 17 人
Nature Mental Health
2026
•2026/5/6
•00 p.1-9
Psychotropic medication use, unhealthy lifestyle behavior and polygenic risk for high BMI (PGS-BMI) may contribute to weight gain and thereby increase cardiovascular disease (CVD) risk in people with mental illness. Using a sample of UK Biobank participants, we examined associations of psychotropic ...
EpidemiologyGenetics researchLifestyle modificationPredictive markersRisk factors
10.1038/S44220-026-00620-W
ISSN:2731-6076
Long-term exposure to residential greenness and decreased risk of depression and anxiety
Jianing Wang•Yudiyang Ma•Linxi Tang•Dankang Li•Junqing Xie等 7 人
Nature Mental Health
2024
•2024/3/28
•00 p.1-10
Residential greenness is considered a unique and potentially modifiable exposure construct to reduce physiological stress and improve human health. Here this study aims to investigate the longitudinal relationships of residential greenness with incident depression and anxiety and to explore and comp...
AnxietyDatabasesDepressionRisk factors
10.1038/S44220-024-00227-Z
ISSN:2731-6076
Activation of FGFR genes by genetic and epigenetic alterations in uterine leiomyomas
Vilja Jokinen•Aurora Taira•Åsa Kolterud•Isa Ahlgren•Kimmo Palin等 18 人
Bjc Reports
2025
•2025/2/27
•Vol.3 No.1 p.1-10
Fibroblast growth factor 1-4 (FGFR1-4) are well-known oncogenic drivers in many cancer types. Here, we studied the role of FGFRs in uterine leiomyoma (UL) that is a benign neoplasm arising from the myometrium and the most common tumour in women. Although ULs can be classified to molecular subtypes b...
Cancer ResearchOncology
10.1038/S44276-025-00127-4
ISSN:2731-9377
Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS
Wouter J. Peyrot•Alkes L. Price
Nature Genetics
2021
•2021/3/8
•00 p.1-10
Psychiatric disorders are highly genetically correlated, but little research has been conducted on the genetic differences between disorders. We developed a new method (case–case genome-wide association study; CC-GWAS) to test for differences in allele frequency between cases of two disorders using ...
Genetic association studyGeneticsPsychiatric disorders
10.1038/S41588-021-00787-1
ISSN:1061-4036
Genetic susceptibility to schizophrenia through neuroinflammatory pathways associated with retinal thinness
Finn Rabe•Lukasz Smigielski•Foivos Georgiadis•Nils Kallen•Wolfgang Omlor等 16 人
Nature Mental Health
2025
•2025/4/21
•00 p.1-10
Schizophrenia is associated with structural and functional changes in the central nervous system, including the most distal part of it, the retina. However, the question of whether retinal atrophy is present before individuals develop schizophrenia or is a secondary consequence of the disorder remai...
Diagnostic markersGenetics researchSchizophrenia
10.1038/S44220-025-00414-6
ISSN:2731-6076
Distinction of lymphoid and myeloid clonal hematopoiesis
Niroula Abhishek•Sekar Aswin•Murakami Mark A.•Trinder Mark•Agrawal Mridul等 15 人
Nature Medicine
2021
•2021/10/18
•00 p.1-7
Clonal hematopoiesis (CH) results from somatic genomic alterations that drive clonal expansion of blood cells. Somatic gene mutations associated with hematologic malignancies detected in hematopoietic cells of healthy individuals, referred to as CH of indeterminate potential (CHIP), have been associ...
Genetics researchHaematological cancer
10.1038/S41591-021-01521-4
ISSN:1078-8956
A prognostic risk score for development and spread of chronic pain
Christophe Tanguay-Sabourin•Matt Fillingim•Gianluca V. Guglietti•Azin Zare•Marc Parisien等 17 人
Nature Medicine
2023
•2023/7/6
•Vol.29 No.7 p.1821-1831
Chronic pain is a complex condition influenced by a combination of biological, psychological and social factors. Using data from the UK Biobank (n = 493,211), we showed that pain spreads from proximal to distal sites and developed a biopsychosocial model that predicted the number of coexisting pain ...
Predictive markersRisk factors
10.1038/S41591-023-02430-4
ISSN:1078-8956
Representational ethical model calibration
Carruthers Robert•Straw Isabel•Ruffle James K.•Herron Daniel•Nelson Amy等 9 人
Npj Digital Medicine
2022
•2022/11/4
•Vol.5 No.1 p.1-9
Equity is widely held to be fundamental to the ethics of healthcare. In the context of clinical decision-making, it rests on the comparative fidelity of the intelligence – evidence-based or intuitive – guiding the management of each individual patient. Though brought to recent attention by the indiv...
Health policyMetabolic disordersTranslational research
10.1038/S41746-022-00716-4
ISSN:2398-6352
Calcium channel blockers increase the risk of aortic aneurysm and dissection
Tianfeng Ma•Zeyu Cai•Xinming Xu•Long Cao•Ao Wang等 20 人
Nature Communications
2025
•2025/12/25
0Aortic aneurysm and dissection (AAD) are life-threatening conditions without effective medications. Impaired contractility of vascular smooth muscle cells (VSMCs) is strongly linked to AAD, but the role of calcium channel blockers (CCBs), which directly inhibits VSMC contractility, in AAD remains un...
Cardiovascular diseasesCell biologyHypertension
10.1038/S41467-025-68086-5
ISSN:2041-1723
On powerful GWAS in admixed populations
Hou Kangcheng•Bhattacharya Arjun•Mester Rachel•Burch Kathryn S.•Pasaniuc Bogdan
Nature Genetics
2021
•2021/11/25
•00 p.1-3
Medical geneticsPopulation genetics
10.1038/S41588-021-00953-5
ISSN:1061-4036
Gene-SGAN: discovering disease subtypes with imaging and genetic signatures via multi-view weakly-supervised deep clustering
Zhijian Yang•Junhao Wen•Ahmed Abdulkadir•Yuhan Cui•Guray Erus等 28 人
Nature Communications
2024
•2024/1/8
•Vol.15 No.1 p.1-16
Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI a...
Computer scienceGenetics researchMachine learningMagnetic resonance imagingNeurodegenerative diseases
10.1038/S41467-023-44271-2
ISSN:2041-1723
Multiomics biomarkers were not superior to clinical variables for pan-cancer screening
Martin Smelik•Yelin Zhao•Dina Mansour Aly•AKM Firoj Mahmud•Oleg Sysoev等 7 人
Communications Medicine
2024
•2024/11/17
•Vol.4 No.1 p.1-8
Cancer screening tests are considered pivotal for early diagnosis and survival. However, the efficacy of these tests for improving survival has recently been questioned. This study aims to test if cancer screening could be improved by biomarkers in peripheral blood based on multi-omics data. We util...
Cancer screeningDiagnostic markers
10.1038/S43856-024-00671-Z
ISSN:2730-664X
An open-source framework for end-to-end analysis of electronic health record data
Lukas Heumos•Philipp Ehmele•Tim Treis•Julius Upmeier zu Belzen•Eljas Roellin等 21 人
Nature Medicine
2024
•2024/9/12
•00 p.1-12
With progressive digitalization of healthcare systems worldwide, large-scale collection of electronic health records (EHRs) has become commonplace. However, an extensible framework for comprehensive exploratory analysis that accounts for data heterogeneity is missing. Here we introduce ehrapy, a mod...
EpidemiologyTranslational research
10.1038/S41591-024-03214-0
ISSN:1078-8956
Neurobiological correlates of schizophrenia-specific and highly pleiotropic genetic risk scores for neuropsychiatric disorders
Lydia M. Federmann•Lisa Sindermann•Sabrina Primus•Federico Raimondo•Konrad Oexle等 16 人
Translational Psychiatry
2025
•2025/7/5
•Vol.15 No.1 p.1-11
Neuropsychiatric disorders show shared and distinct neurobiological correlates. A cross-disorder genome-wide association study (GWAS) identified 23 highly pleiotropic single-nucleotide polymorphisms (SNPs) that were associated with at least four neuropsychiatric disorders, and 22 SNPs that were asso...
GeneticsNeurosciencePsychiatric disorders
10.1038/S41398-025-03440-1
ISSN:2158-3188
Adipose tissue eQTL meta-analysis highlights the contribution of allelic heterogeneity to gene expression regulation and cardiometabolic traits
Sarah M. Brotman•Julia S. El-Sayed Moustafa•Li Guan•K. Alaine Broadaway•Dongmeng Wang等 34 人
Nature Genetics
2025
•2025/1/2
•00 p.1-13
Complete characterization of the genetic effects on gene expression is needed to elucidate tissue biology and the etiology of complex traits. In the present study, we analyzed 2,344 subcutaneous adipose tissue samples and identified 34,774 conditionally distinct expression quantitative trait locus (...
Cardiovascular diseasesGene expressionTranscriptomics
10.1038/S41588-024-01982-6
ISSN:1061-4036
Genetically personalised organ-specific metabolic models in health and disease
Foguet Carles•Xu Yu•Ritchie Scott C.•Lambert Samuel A.•Persyn Elodie等 14 人
Nature Communications
2022
•2022/11/29
•Vol.13 No.1 p.1-15
Understanding how genetic variants influence disease risk and complex traits (variant-to-function) is one of the major challenges in human genetics. Here we present a model-driven framework to leverage human genome-scale metabolic networks to define how genetic variants affect biochemical reaction f...
Biochemical networksCardiovascular diseasesMetabolomics
10.1038/S41467-022-35017-7
ISSN:2041-1723
Lossless integration of multiple electronic health records for identifying pleiotropy using summary statistics
Ruowang Li•Rui Duan•Xinyuan Zhang•Thomas Lumley•Sarah Pendergrass等 19 人
Nature Communications
2021
•2021/1/8
•Vol.12 No.1 p.1-10
Increasingly, clinical phenotypes with matched genetic data from bio-bank linked electronic health records (EHRs) have been used for pleiotropy analyses. Thus far, pleiotropy analysis using individual-level EHR data has been limited to data from one site. However, it is desirable to integrate EHR da...
Data integrationStatistical methods
10.1038/S41467-020-20211-2
ISSN:2041-1723
Exploring the genetic and genomic connection underlying neurodegeneration with brain iron accumulation and the risk for Parkinson’s disease
Alvarez Jerez Pilar•Alcantud Jose Luis•de los Reyes-Ramírez Lucia•Moore Anni•Ruz Clara等 17 人
Npj Parkinson's Disease
2023
•2023/4/6
•Vol.9 No.1 p.1-9
Neurodegeneration with brain iron accumulation (NBIA) represents a group of neurodegenerative disorders characterized by abnormal iron accumulation in the brain. In Parkinson’s Disease (PD), iron accumulation is a cardinal feature of degenerating regions in the brain and seems to be a key player in ...
Genetic association studyGenomics
10.1038/S41531-023-00496-Y
ISSN:2373-8057
Dynamic regulatory elements in single-cell multimodal data implicate key immune cell states enriched for autoimmune disease heritability
Anika Gupta•Kathryn Weinand•Aparna Nathan•Saori Sakaue•Martin Jinye Zhang等 10 人
Nature Genetics
2023
•2023/11/30
•00 p.1-11
In autoimmune diseases such as rheumatoid arthritis, the immune system attacks the body’s own cells. Developing a precise understanding of the cell states where noncoding autoimmune risk variants impart causal mechanisms is critical to developing curative therapies. Here, to identify noncoding regio...
Computational biology and bioinformaticsEpigenomicsImmunogenetics
10.1038/S41588-023-01577-7
ISSN:1061-4036
Associations of clinical biomarker-based biological aging with suicide attempts and suicidal ideation: evidence from 124,529 UK Biobank participants
Wei Hu•Zhenzhen Shen•Ge Tian•Baopeng Liu•Cunxian Jia
Translational Psychiatry
2025
•2025/6/18
•Vol.15 No.1 p.1-9
Biological aging has been linked to multiple psychological disorders, yet its extrapolation to suicide remains absent. We aimed to examine the associations of biological aging with suicidal ideation (SI) and suicide attempt (SA) and to explore possible moderators of the associations. A total of 124,...
Predictive markersPsychiatric disorders
10.1038/S41398-025-03412-5
ISSN:2158-3188
Common variants contribute to intrinsic human brain functional networks
Zhao Bingxin•Li Tengfei•Smith Stephen M.•Xiong Di•Wang Xifeng等 20 人
Nature Genetics
2022
•2022/4/7
•00 p.1-10
The human brain forms functional networks of correlated activity, which have been linked with both cognitive and clinical outcomes. However, the genetic variants affecting brain function are largely unknown. Here, we used resting-state functional magnetic resonance images from 47,276 individuals to ...
Genome-wide association studiesNeuroscience
10.1038/S41588-022-01039-6
ISSN:1061-4036
Nexus between residential air pollution and physiological stress is moderated by greenness
Ka Yan Lai•Sarika Kumari•John Gallacher•Chris Webster•Chinmoy Sarkar
Nature Cities
2024
•2024/2/16
•00 p.1-13
Urban living is synonymous with a higher exposure to environmental stressors such as air pollution and associated physiological stress; however, the modifying role of greenness has been understudied. We included 190,200 participants from a UK-wide cohort to examine the modifying role of residential ...
Psychology and behaviourPublic healthSigns and symptoms
10.1038/S44284-024-00036-6
ISSN:2731-9997
A sex-specific genome-wide association study of depression phenotypes in UK Biobank
Silveira Patrícia Pelufo•Pokhvisneva Irina•Howard David M.•Meaney Michael J.
Molecular Psychiatry
2023
•2023/2/7
•00 p.1-11
There are marked sex differences in the prevalence, phenotypic presentation and treatment response for major depression. While genome-wide association studies (GWAS) adjust for sex differences, to date, no studies seek to identify sex-specific markers and pathways. In this study, we performed a sex-...
DepressionGenetics
10.1038/S41380-023-01960-0
ISSN:1359-4184
Validity of European-centric cardiometabolic polygenic scores in multi-ancestry populations
Constantin-Cristian Topriceanu•Nish Chaturvedi•Rohini Mathur•Victoria Garfield
European Journal Of Human Genetics
2024
•2024/1/5
•00 p.1-11
Polygenic scores (PGSs) provide an individual level estimate of genetic risk for any given disease. Since most PGSs have been derived from genome wide association studies (GWASs) conducted in populations of White European ancestry, their validity in other ancestry groups remains unconfirmed. This is...
Disease preventionRisk factors
10.1038/S41431-023-01517-3
ISSN:1018-4813
Estimation and mapping of the missing heritability of human phenotypes
Pierrick Wainschtein•Yuanxiang Zhang•Jeremy Schwartzentruber•Irfahan Kassam•Julia Sidorenko等 16 人
Nature
2025
•2025/11/12
•00 p.1-9
Rare coding variants shape inter-individual differences in human phenotypes1. However, the contribution of rare non-coding variants to those differences remains poorly characterized. Here we analyse whole-genome sequence (WGS) data from 347,630 individuals with European ancestry in the UK Biobank2,3...
Genome-wide association studiesPopulation geneticsQuantitative trait lociRare variants
10.1038/S41586-025-09720-6
ISSN:0028-0836
Multi-resolution localization of causal variants across the genome
Matteo Sesia•Eugene Katsevich•Stephen Bates•Emmanuel Candès•Chiara Sabatti
Nature Communications
2020
•2020/2/27
•Vol.11 No.1 p.1-10
In the statistical analysis of genome-wide association data, it is challenging to precisely localize the variants that affect complex traits, due to linkage disequilibrium, and to maximize power while limiting spurious findings. Here we report on KnockoffZoom: a flexible method that localizes causal...
Genetic variationGenome-wide association studiesHaplotypesStatistical methods
10.1038/S41467-020-14791-2
ISSN:2041-1723
The interaction and mediation role of intrinsic capacity in the association between asthma and all-cause mortality
Yangyang Cheng•Yue Zhang•Junjie Lin•Chenjie Xu•Xiaolin Xu
Npj Primary Care Respiratory Medicine
2025
•2025/11/24
•Vol.35 No.1 p.540
Asthma and intrinsic capacity (IC) decline were individually examined with mortality, yet the complex interplay between them remains largely unknown. This study aimed to examine the potential roles of IC decline in the association between asthma and all-cause mortality. We conducted a prospective co...
EpidemiologyImmunological disordersRespiratory tract diseases
10.1038/S41533-025-00459-1
ISSN:2055-1010
Improved genetic prediction of complex traits from individual-level data or summary statistics
Qianqian Zhang•Florian Privé•Bjarni Vilhjálmsson•Doug Speed
Nature Communications
2021
•2021/7/7
•Vol.12 No.1 p.1-9
Most existing tools for constructing genetic prediction models begin with the assumption that all genetic variants contribute equally towards the phenotype. However, this represents a suboptimal model for how heritability is distributed across the genome. Therefore, we develop prediction tools that ...
Genetic association studyHeritable quantitative traitQuantitative traitStatistical methods
10.1038/S41467-021-24485-Y
ISSN:2041-1723
Trends in incident diagnoses and drug prescriptions for anxiety and depression during the COVID-19 pandemic: an 18-month follow-up study based on the UK Biobank
Wang Yue•Ge Fenfen•Wang Junren•Yang Huazhen•Han Xin等 15 人
Translational Psychiatry
2023
•2023/1/19
•Vol.13 No.1 p.1-8
Serious concerns have been raised about the negative effects of the COVID-19 pandemic on population psychological well-being. However, limited data exist on the long-term effects of the pandemic on incident psychiatric morbidities among individuals with varying exposure to the pandemic. Leveraging p...
DepressionPsychiatric disorders
10.1038/S41398-023-02315-7
ISSN:2158-3188
A biobank-scale test of marginal epistasis reveals genome-wide signals of polygenic interaction effects
Boyang Fu•Ali Pazokitoroudi•Zhuozheng Shi•Asha Kar•Albert Xue等 12 人
Nature Genetics
2025
•2025/12/9
•Vol.57 No.12 p.3175-3184
The contribution of genetic interactions (epistasis) to human complex trait variation remains poorly understood due, in part, to the statistical and computational challenges involved in testing for interaction effects. Here we introduce FAME (FAst Marginal Epistasis test), a method that can test for...
Genome-wide association studiesSoftware
10.1038/S41588-025-02411-Y
ISSN:1061-4036
African-ancestry-specific variant IKKβ p.Glu502Lys confers high lupus risk
Gudny Ella Thorlacius•Erna V. Ivarsdottir•Saedis Saevarsdottir•Kristjan H. S. Moore•Sigurjon A. Gudjonsson等 29 人
Nature Genetics
2025
•2025/11/17
•00 p.1-7
Cutaneous lupus erythematosus (CLE) is an autoimmune disease of the skin, occurring with or without systemic lupus erythematosus (SLE). People with African ancestry have a higher risk than people with other ancestries of developing lupus1 but have been underrepresented in genetic studies. We whole-g...
Genome-wide association studiesSystemic lupus erythematosus
10.1038/S41588-025-02398-6
ISSN:1061-4036
Identifying multiple sclerosis subtypes using unsupervised machine learning and MRI data
Arman Eshaghi•Alexandra L. Young•Peter A. Wijeratne•Ferran Prados•Douglas L. Arnold等 12 人
Nature Communications
2021
•2021/4/6
•Vol.12 No.1 p.1-12
Multiple sclerosis (MS) can be divided into four phenotypes based on clinical evolution. The pathophysiological boundaries of these phenotypes are unclear, limiting treatment stratification. Machine learning can identify groups with similar features using multidimensional data. Here, to classify MS ...
Functional magnetic resonance imagingLearning algorithmsMultiple sclerosis
10.1038/S41467-021-22265-2
ISSN:2041-1723
Whole-genome sequencing of patients with rare diseases in a national health system
Ernest Turro•William J. Astle•Karyn Megy•Stefan Gräf•Daniel Greene等 53 人
Nature
2020
•2020/6/24
•Vol.583 No.7814 p.96-102
Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown a...
Computational biology and bioinformaticsDisease geneticsGenetics research
10.1038/S41586-020-2434-2
ISSN:0028-0836
Reproducible brain-wide association studies require thousands of individuals
Marek Scott•Tervo-Clemmens Brenden•Calabro Finnegan J.•Montez David F.•Kay Benjamin P.等 45 人
Nature
2022
•2022/3/16
•00 p.1-7
Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions1–3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize simi...
Cognitive neurosciencePsychology
10.1038/S41586-022-04492-9
ISSN:0028-0836
Metabolic profiling reveals circulating biomarkers associated with incident and prevalent Parkinson’s disease
Wenyi Hu•Wei Wang•Huan Liao•Gabriella Bulloch•Xiayin Zhang等 12 人
Npj Parkinson's Disease
2024
•2024/7/9
•Vol.10 No.1 p.1-8
The metabolic profile predating the onset of Parkinson’s disease (PD) remains unclear. We aim to investigate the metabolites associated with incident and prevalent PD and their predictive values in the UK Biobank participants with metabolomics and genetic data at the baseline. A panel of 249 metabol...
Parkinson's diseasePredictive markers
10.1038/S41531-024-00713-2
ISSN:2373-8057
Analysis of rare genetic variation underlying cardiometabolic diseases and traits among 200,000 individuals in the UK Biobank
Jurgens Sean J.•Choi Seung Hoan•Morrill Valerie N.•Chaffin Mark•Pirruccello James P.等 18 人
Nature Genetics
2022
•2022/2/17
•00 p.1-11
Cardiometabolic diseases are the leading cause of death worldwide. Despite a known genetic component, our understanding of these diseases remains incomplete. Here, we analyzed the contribution of rare variants to 57 diseases and 26 cardiometabolic traits, using data from 200,337 UK Biobank participa...
Cardiovascular diseasesDNA sequencingGenetics researchPopulation genetics
10.1038/S41588-021-01011-W
ISSN:1061-4036
A tissue-level phenome-wide network map of colocalized genes and phenotypes in the UK Biobank
Rocheleau Ghislain•Forrest Iain S.•Duffy Áine•Bafna Shantanu•Dobbyn Amanda等 9 人
Communications Biology
2022
•2022/8/20
•Vol.5 No.1 p.1-9
Phenome-wide association studies identified numerous loci associated with traits and diseases. To help interpret these associations, we constructed a phenome-wide network map of colocalized genes and phenotypes. We generated colocalized signals using the Genotype-Tissue Expression data and genome-wi...
Gene expressionMedical genomics
10.1038/S42003-022-03820-Z
ISSN:2399-3642
Genome-wide association study of thoracic aortic aneurysm and dissection in the Million Veteran Program
Derek Klarin•Poornima Devineni•Anoop K. Sendamarai•Anthony R. Angueira•Sarah E. Graham等 36 人
Nature Genetics
2023
•2023/6/12
•00 p.1-10
The current understanding of the genetic determinants of thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies of rare, Mendelian forms of disease. Here, we conducted a genome-wide association study (GWAS) of TAAD, testing ~25 million DNA sequence variants in 8,6...
Computational biology and bioinformaticsGenome-wide association studies
10.1038/S41588-023-01420-Z
ISSN:1061-4036
Genetic architecture reconciles linkage and association studies of complex traits
Julia Sidorenko•Baptiste Couvy-Duchesne•Kathryn E. Kemper•Gunn-Helen Moen•Laxmi Bhatta等 27 人
Nature Genetics
2024
•2024/10/7
•00 p.1-9
Linkage studies have successfully mapped loci underlying monogenic disorders, but mostly failed when applied to common diseases. Conversely, genome-wide association studies (GWASs) have identified replicable associations between thousands of SNPs and complex traits, yet capture less than half of the...
Genetic linkage studyGenome-wide association studies
10.1038/S41588-024-01940-2
ISSN:1061-4036
Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries
Puya Gharahkhani•Eric Jorgenson•Pirro Hysi•Anthony P. Khawaja•Sarah Pendergrass等 79 人
Nature Communications
2021
•2021/2/24
•Vol.12 No.1 p.1-16
Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirm...
Genome-wide association studiesOptic nerve diseases
10.1038/S41467-020-20851-4
ISSN:2041-1723
Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits
Nora Scherer•Daniel Fässler•Oleg Borisov•Yurong Cheng•Pascal Schlosser等 29 人
Nature Genetics
2025
•2025/1/2
•00 p.1-13
Genetic studies of the metabolome can uncover enzymatic and transport processes shaping human metabolism. Using rare variant aggregation testing based on whole-exome sequencing data to detect genes associated with levels of 1,294 plasma and 1,396 urine metabolites, we discovered 235 gene–metabolite ...
EpidemiologyGenetic association studyGenetics researchMetabolomicsPopulation genetics
10.1038/S41588-024-01965-7
ISSN:1061-4036
Concordance between male- and female-specific GWAS results helps define underlying genetic architecture of complex traits
Anna K. Miller•Jacquelaine Bartlett•Calvin Pan•Aldons J. Lusis•Dana C. Crawford等 7 人
Nature Communications
2025
•2025/9/30
•Vol.16 No.1 p.1-12
A better understanding of genetic architecture will help enhance precision medicine and clinical care. Towards this end, we investigate sex-stratified analyses for several traits in the Hybrid Mouse Diversity Panel (HMDP) and UK Biobank to assess trait polygenicity and identify contributing loci. By...
EpistasisGenome-wide association studiesObesityType 2 diabetes
10.1038/S41467-025-63763-X
ISSN:2041-1723
Indirect assortative mating for human disease and longevity
Konrad Rawlik•Oriol Canela-Xandri•Albert Tenesa
Heredity
2019
•2019/2/5
•Vol.123 No.2 p.106-116
Phenotypic correlations among partners for traits such as longevity or late-onset disease have been found to be comparable to phenotypic correlations in first-degree relatives. How these correlations arise in late life is poorly understood. Here we introduce a novel paradigm to establish the presenc...
EvolutionGenetics
10.1038/S41437-019-0185-3
ISSN:0018-067X
Genetic architectures of cerebral ventricles and their overlap with neuropsychiatric traits
Yi-Jun Ge•Bang-Sheng Wu•Yi Zhang•Shi-Dong Chen•Ya-Ru Zhang等 43 人
Nature Human Behaviour
2023
•2023/10/19
•00 p.1-17
The cerebral ventricles are recognized as windows into brain development and disease, yet their genetic architectures, underlying neural mechanisms and utility in maintaining brain health remain elusive. Here we aggregated genetic and neuroimaging data from 61,974 participants (age range, 9 to 98 ye...
Alzheimer's diseaseGenetics of the nervous systemGenetics researchGenome-wide association studies
10.1038/S41562-023-01722-6
ISSN:2397-3374
GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements
Dixon Peter H.•Levine Adam P.•Cebola Inês•Chan Melanie M. Y.•Amin Aliya S.等 22 人
Nature Communications
2022
•2022/8/17
•Vol.13 No.1 p.1-18
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse o...
Gene expression profilingGenome-wide association studiesLiver diseases
10.1038/S41467-022-29931-Z
ISSN:2041-1723
Genome-wide meta-analysis identifies 22 loci for normal tension glaucoma with significant overlap with high tension glaucoma
Santiago Diaz-Torres•Weixiong He•Regina Yu•Anthony P. Khawaja•Christopher J. Hammond等 22 人
Nature Communications
2024
•2024/11/17
•Vol.15 No.1 p.1-9
Primary open-angle glaucoma typically presents as two subtypes. This study aimed to elucidate the shared and distinct genetic architectures of normal-tension (NTG) and high-tension glaucoma (HTG), motivated by the need to develop intraocular pressure (IOP)-independent drug targets for the disease. W...
Drug discoveryGenome-wide association studiesOptic nerve diseases
10.1038/S41467-024-54301-2
ISSN:2041-1723
The current state of polygenic scores for the development of lung cancer: a systematic review and validation in UK Biobank
Bayan Galal•Joe Dennis•Antonis C. Antoniou•Hannah Harrison
British Journal Of Cancer
2026
•2026/1/8
•Vol.134 No.6 p.939-948
Risk-stratified lung cancer screening programs identify high-risk individuals who use tobacco but do not account for underlying genetic susceptibility. Many polygenic scores (PGS) have been developed for lung cancer, but it is unclear which, if any, are suitable for identifying high-risk individuals...
Lung cancerRisk factors
10.1038/S41416-025-03330-9
ISSN:0007-0920
FAIRly big: A framework for computationally reproducible processing of large-scale data
Wagner Adina S.•Waite Laura K.•Wierzba Małgorzata•Hoffstaedter Felix•Waite Alexander Q.等 8 人
Scientific Data
2022
•2022/3/11
•Vol.9 No.1 p.1-17
Large-scale datasets present unique opportunities to perform scientific investigations with unprecedented breadth. However, they also pose considerable challenges for the findability, accessibility, interoperability, and reusability (FAIR) of research outcomes due to infrastructure limitations, data...
Data processingData publication and archivingSoftware
10.1038/S41597-022-01163-2
ISSN:2052-4463
Associations between alcohol consumption and gray and white matter volumes in the UK Biobank
Daviet Remi•Aydogan Gökhan•Jagannathan Kanchana•Spilka Nathaniel•Koellinger Philipp D.等 8 人
Nature Communications
2022
•2022/3/4
•Vol.13 No.1 p.1-11
Heavy alcohol consumption has been associated with brain atrophy, neuronal loss, and poorer white matter fiber integrity. However, there is conflicting evidence on whether light-to-moderate alcohol consumption shows similar negative associations with brain structure. To address this, we examine the ...
NeurologyNeuroscience
10.1038/S41467-022-28735-5
ISSN:2041-1723
An enhanced framework for local genetic correlation analysis
Yuying Li•Yudi Pawitan•Xia Shen
Nature Genetics
2025
•2025/3/10
•00 p.1-6
Genetic correlation is a key parameter in the joint genetic model of complex traits, but it is usually estimated on a global genomic scale. Understanding local genetic correlations provides more detailed insight into the shared genetic architecture of complex traits. However, a state-of-the-art tool...
Genome-wide association studiesHigh-throughput screening
10.1038/S41588-025-02123-3
ISSN:1061-4036
Serum 25-hydroxyvitamin D concentrations and colorectal cancer incidence in adults with type 2 diabetes
Jiao-Jiao Ren•Zhi-Hao Li•Wen-Fang Zhong•Pei-Liang Chen•Qing-Mei Huang等 8 人
British Journal Of Cancer
2023
•2023/6/19
•00 p.1-6
To examine the association of serum 25-hydroxyvitamin D (25[OH]D) with colorectal cancer (CRC) risk in adults with type 2 diabetes (T2D). Using UK Biobank data, this study included 18,453 adults with T2D. Serum 25(OH)D concentrations were determined by the chemiluminescent immunoassay method. A Cox ...
Cancer epidemiologyDiabetes complicationsMalnutrition
10.1038/S41416-023-02323-W
ISSN:0007-0920
Trans-ethnic association study of blood pressure determinants in over 750,000 individuals
Ayush Giri•Jacklyn N. Hellwege•Jacob M. Keaton•Jihwan Park•Chengxiang Qiu等 53 人
Nature Genetics
2018
•2018/12/21
•Vol.51 No.1 p.51-62
In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of s...
Gene expressionGene regulationGenome-wide association studiesHypertension
10.1038/S41588-018-0303-9
ISSN:1061-4036
Widespread signatures of natural selection across human complex traits and functional genomic categories
Jian Zeng•Angli Xue•Longda Jiang•Luke R. Lloyd-Jones•Yang Wu等 13 人
Nature Communications
2021
•2021/2/19
•Vol.12 No.1 p.1-12
Understanding how natural selection has shaped genetic architecture of complex traits is of importance in medical and evolutionary genetics. Bayesian methods have been developed using individual-level GWAS data to estimate multiple genetic architecture parameters including selection signature. Here,...
Genetic variationGenome-wide association studiesQuantitative trait
10.1038/S41467-021-21446-3
ISSN:2041-1723
A Mendelian randomization study of IL6 signaling in cardiovascular diseases, immune-related disorders and longevity
Mickael Rosa•Arnaud Chignon•Zhonglin Li•Marie-Chloé Boulanger•Benoit J. Arsenault等 8 人
Npj Genomic Medicine
2019
•2019/9/20
•Vol.4 No.1 p.1-10
Growing evidence suggests that inflammation is a significant contributor to different cardiovascular diseases (CVDs). Mendelian randomization (MR) was performed to assess the causal inference between plasma soluble IL6 receptor (sIL6R), a negative regulator of IL6 signaling, and different cardiovasc...
Cardiovascular diseasesGenetics research
10.1038/S41525-019-0097-4
ISSN:2056-7944
RSPO3 is important for trabecular bone and fracture risk in mice and humans
Nilsson Karin H.•Henning Petra•Shahawy Maha El•Nethander Maria•Andersen Thomas Levin等 21 人
Nature Communications
2021
•2021/8/13
•Vol.12 No.1 p.1-18
With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture...
BoneOsteoblasts
10.1038/S41467-021-25124-2
ISSN:2041-1723
HTRA1/lncRNA HTRA1-AS1 dominates in age-related macular degeneration reticular pseudodrusen genetic risk with no complement involvement
Samaneh Farashi•Carla J. Abbott•Brendan R. E. Ansell•Zhichao Wu•Lebriz Altay等 49 人
Nature Communications
2025
•2025/12/8
•Vol.16 No.1 p.108540
Age-related macular degeneration (AMD) is a multifactorial retinal disease with a large genetic risk contribution. Reticular pseudodrusen (RPD) is a sub-phenotype of AMD with a high risk of progression to late vision threatening AMD. In a genome-wide association study of 2165 AMD+/RPD+ and 4181 AMD+...
DNA sequencingGenome-wide association studiesMacular degenerationRNA sequencing
10.1038/S41467-025-65903-9
ISSN:2041-1723
An atlas of genetic determinants of forearm fracture
Maria Nethander•Sofia Movérare-Skrtic•Anders Kämpe•Eivind Coward•Ene Reimann等 35 人
Nature Genetics
2023
•2023/11/2
•Vol.55 No.11 p.1820-1830
Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are the most common clinically recognized osteoporotic fractures with a relatively high heritability. To establish an atlas of the gene...
Genetics researchTranslational research
10.1038/S41588-023-01527-3
ISSN:1061-4036
Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis
Simon N. Stacey•Florian Zink•Gisli H. Halldorsson•Lilja Stefansdottir•Sigurjon A. Gudjonsson等 31 人
Nature Genetics
2023
•2023/11/6
•00 p.1-11
Clonal hematopoiesis (CH) arises when a substantial proportion of mature blood cells is derived from a single hematopoietic stem cell lineage. Using whole-genome sequencing of 45,510 Icelandic and 130,709 UK Biobank participants combined with a mutational barcode method, we identified 16,306 people ...
AgeingGenome-wide association studiesMyelodysplastic syndrome
10.1038/S41588-023-01555-Z
ISSN:1061-4036
A Representation Fusion Framework for Decoupling Diagnostic Information in Multimodal Learning
Sana Tonekaboni•Sam Freesun Friedman•Xinyi Zhang•Mahnaz Maddah•Caroline Uhler
Npj Digital Medicine
2025
•2025/12/17
•Vol.8 No.1 p.7650
Modern medicine increasingly relies on multimodal data, ranging from clinical notes to imaging and genomics, to guide diagnosis and treatment. However, integrating these heterogeneous data sources in a principled and interpretable manner remains a major challenge. We present MODES (Multi-mOdal Disen...
BiomarkersComputational biology and bioinformaticsComputational scienceHealth care
10.1038/S41746-025-02144-6
ISSN:2398-6352
Improving polygenic score prediction for underrepresented groups through transfer learning
Hao Wu•Paulino Pérez-Rodríguez•Michael Boehnke•Yuehua Cui•Xiaoyu Liang等 7 人
Nature Communications
2026
•2026/1/23
•Vol.17 No.1 p.19730
The advent of large biobanks has substantially increased the accuracy of polygenic scores (PGS). However, most existing PGSs were derived from European-ancestry data and often exhibit reduced predictive performance when applied to individuals of non-European ancestries. Transfer Learning offers a pr...
Computational modelsGenomicsSoftwareStatistical methods
10.1038/S41467-026-68696-7
ISSN:2041-1723
A method to estimate the contribution of rare coding variants to complex trait heritability
Nazia Pathan•Wei Q. Deng•Matteo Di Scipio•Mohammad Khan•Shihong Mao等 10 人
Nature Communications
2024
•2024/2/9
•Vol.15 No.1 p.1-16
It has been postulated that rare coding variants (RVs; MAF < 0.01) contribute to the “missing” heritability of complex traits. We developed a framework, the Rare variant heritability (RARity) estimator, to assess RV heritability (h2RV) without assuming a particular genetic architecture. We applie...
Diagnostic markersMedical genomicsNext-generation sequencingRare variantsStatistical methods
10.1038/S41467-024-45407-8
ISSN:2041-1723
MultiSuSiE improves multi-ancestry fine-mapping in All of Us whole-genome sequencing data
Jordan Rossen•Huwenbo Shi•Benjamin J. Strober•Martin Jinye Zhang•Masahiro Kanai等 9 人
Nature Genetics
2026
•2026/1/5
•Vol.58 No.1 p.67-76
Leveraging multi-ancestry data can improve fine-mapping power. We propose MultiSuSiE, an extension of Sum of Single Effects (SuSiE), to multiple ancestries that allows causal effect sizes to vary across ancestries. We evaluated MultiSuSiE using whole-genome sequencing data from 47,000 African-ancest...
SequencingSoftware
10.1038/S41588-025-02450-5
ISSN:1061-4036
Imaging genetics of language network functional connectivity reveals links with language-related abilities, dyslexia and handedness
Jitse S. Amelink•Merel C. Postema•Xiang-Zhen Kong•Dick Schijven•Amaia Carrión-Castillo等 11 人
Communications Biology
2024
•2024/9/28
•Vol.7 No.1 p.1-13
Language is supported by a distributed network of brain regions with a particular contribution from the left hemisphere. A multi-level understanding of this network requires studying its genetic architecture. We used resting-state imaging data from 29,681 participants (UK Biobank) to measure connect...
Genetics of the nervous systemGenome-wide association studies
10.1038/S42003-024-06890-3
ISSN:2399-3642
Genetic liability to major psychiatric disorders contributes to multi-faceted quality of life outcomes in children and adults
Yingjie Shi•Nina Roth Mota•Barbara Franke•Emma Sprooten
Translational Psychiatry
2025
•2025/7/7
•Vol.15 No.1 p.1-8
Psychiatric conditions, known for their hereditary nature, exert significant impacts on various life domains. Leveraging this heritability, we examine the relations between genetic susceptibility to major psychiatric disorders and the multifaceted aspects of quality of life in two population-based c...
GenomicsPsychiatric disorders
10.1038/S41398-025-03443-Y
ISSN:2158-3188
Mendelian randomisation analysis of the effect of educational attainment and cognitive ability on smoking behaviour
Eleanor Sanderson•George Davey Smith•Jack Bowden•Marcus R. Munafò
Nature Communications
2019
•2019/7/3
•Vol.10 No.1 p.1-9
Recent analyses have shown educational attainment to be associated with a number of health outcomes. This association may, in part, be due to an effect of educational attainment on smoking behaviour. In this study, we apply a multivariable Mendelian randomisation design to determine whether the effe...
EducationEpidemiologyGenome-wide association studiesHuman behaviour
10.1038/S41467-019-10679-Y
ISSN:2041-1723
MESuSiE enables scalable and powerful multi-ancestry fine-mapping of causal variants in genome-wide association studies
Boran Gao•Xiang Zhou
Nature Genetics
2024
•2024/1/2
•00 p.1-10
Fine-mapping in genome-wide association studies attempts to identify causal SNPs from a set of candidate SNPs in a local genomic region of interest and is commonly performed in one genetic ancestry at a time. Here, we present multi-ancestry sum of the single effects model (MESuSiE), a probabilistic ...
Genome-wide association studiesSoftware
10.1038/S41588-023-01604-7
ISSN:1061-4036
Theoretical and empirical quantification of the accuracy of polygenic scores in ancestry divergent populations
Ying Wang•Jing Guo•Guiyan Ni•Jian Yang•Peter M. Visscher等 6 人
Nature Communications
2020
•2020/7/31
•Vol.11 No.1 p.1-9
Polygenic scores (PGS) have been widely used to predict disease risk using variants identified from genome-wide association studies (GWAS). To date, most GWAS have been conducted in populations of European ancestry, which limits the use of GWAS-derived PGS in non-European ancestry populations. Here,...
Genetic variationGenome-wide association studiesStatistical methods
10.1038/S41467-020-17719-Y
ISSN:2041-1723
Association between multimorbidity status and incident dementia: a prospective cohort study of 245,483 participants
Hu He-Ying•Zhang Ya-Ru•Aerqin Qiaolifan•Ou Ya-Nan•Wang Zuo-Teng等 9 人
Translational Psychiatry
2022
•2022/12/7
•Vol.12 No.1 p.1-10
Multimorbidity (the presence of two or more long-term conditions [LTCs]) was suggested to exacerbate the neuronal injuries. The impact of multimorbidity on dementia has not been fully elucidated. We aimed to investigate the association between multimorbidity and dementia risk. We used the prospectiv...
DiseasesPsychiatric disorders
10.1038/S41398-022-02268-3
ISSN:2158-3188
Normal weight obesity, circulating biomarkers and risk of breast cancer: a prospective cohort study and meta-analysis
Wenjie Wang•Xiaoyan Wang•Ying Jiang•Yingying Guo•Peifen Fu等 7 人
British Journal Of Cancer
2024
•2024/11/28
•00 p.1-9
Individuals with normal weight obesity (NWO) often escape the attention of healthcare providers who may assume that a normal body mass index (BMI) correlates with low health risks. However, it remains unknown whether NWO increases the risk of breast cancer. This study included 22,257 and 52,506 pre-...
Breast cancerPublic healthWeight management
10.1038/S41416-024-02906-1
ISSN:0007-0920
Genome-first determination of the prevalence and penetrance of eight germline myeloid malignancy predisposition genes: a study of two population-based cohorts
Rachel M. Hendricks•Jung Kim•Jeremy S. Haley•Mark Louie Ramos•Uyenlinh L. Mirshahi等 8 人
Leukemia
2024
•2024/11/6
•00 p.1-12
It is estimated that 10% of individuals with a myeloid malignancy carry a germline susceptibility. Using the genome-first approach, in which individuals were ascertained on genotype alone, rather than clinical phenotype, we quantified the prevalence and penetrance of pathogenic germline variants in ...
Cancer geneticsRisk factors
10.1038/S41375-024-02436-Y
ISSN:0887-6924
Titin truncating variants, cardiovascular risk factors and the risk of atrial fibrillation and heart failure
Naman S. Shetty•Mokshad Gaonkar•Akhil Pampana•Nirav Patel•Peng Li等 7 人
Nature Cardiovascular Research
2024
•2024/7/31
•00 p.1-8
High-proportion spliced-in (hiPSI) titin truncating variant (TTNtv) carriers have a higher risk of atrial fibrillation and heart failure1. However, the role of cardiovascular risk factors in modifying the risk of atrial fibrillation and heart failure attributed to hiPSI TTNtv carriers is unknown. He...
CardiologyDisease geneticsGenetic association studyGenetics research
10.1038/S44161-024-00511-2
ISSN:2731-0590
Functionally informed fine-mapping and polygenic localization of complex trait heritability
Omer Weissbrod•Farhad Hormozdiari•Christian Benner•Ran Cui•Jacob Ulirsch等 14 人
Nature Genetics
2020
•2020/11/16
•Vol.52 No.12 p.1355-1363
Fine-mapping aims to identify causal variants impacting complex traits. We propose PolyFun, a computationally scalable framework to improve fine-mapping accuracy by leveraging functional annotations across the entire genome—not just genome-wide-significant loci—to specify prior probabilities for fin...
Functional genomicsGenome-wide association studies
10.1038/S41588-020-00735-5
ISSN:1061-4036
Fast kernel-based association testing of non-linear genetic effects for biobank-scale data
Boyang Fu•Ali Pazokitoroudi•Mukund Sudarshan•Zhengtong Liu•Lakshminarayanan Subramanian等 6 人
Nature Communications
2023
•2023/8/15
•Vol.14 No.1 p.1-8
Our knowledge of non-linear genetic effects on complex traits remains limited, in part, due to the modest power to detect such effects. While kernel-based tests offer a versatile approach to test for non-linear relationships between sets of genetic variants and traits, current approaches cannot be a...
Computational modelsEpistasis
10.1038/S41467-023-40346-2
ISSN:2041-1723
Cross-modal autoencoder framework learns holistic representations of cardiovascular state
Radhakrishnan Adityanarayanan•Friedman Sam F.•Khurshid Shaan•Ng Kenney•Batra Puneet等 8 人
Nature Communications
2023
•2023/4/28
•Vol.14 No.1 p.1-12
A fundamental challenge in diagnostics is integrating multiple modalities to develop a joint characterization of physiological state. Using the heart as a model system, we develop a cross-modal autoencoder framework for integrating distinct data modalities and constructing a holistic representation ...
Computer scienceData integrationGenome-wide association studiesMachine learning
10.1038/S41467-023-38125-0
ISSN:2041-1723
Accelerometer-derived physical activity and mortality in individuals with type 2 diabetes
Zhi Cao•Jiahao Min•Han Chen•Yabing Hou•Hongxi Yang等 7 人
Nature Communications
2024
•2024/6/17
•Vol.15 No.1 p.1-11
Physical activity (PA) has been shown to reduce diabetes mortality, but largely based on imprecise self-reported data, which may hinder the development of related recommendations. Here, we perform a prospective cohort study of 19,624 individuals with type 2 diabetes (T2D) from the UK Biobank with a ...
Public healthRisk factorsType 2 diabetes
10.1038/S41467-024-49542-0
ISSN:2041-1723
A study of the associations between social isolation and loneliness with sex-specific cancer risk in the UK Biobank
Jiahao Cheng•Runchen Wang•Yi Feng•Shijie Ye•Hengrui Liang等 16 人
Communications Medicine
2026
•2026/3/2
•Vol.6 No.1 p.2000
Social isolation, an objective lack of social connections, and loneliness, the subjective distress from perceived social deficits, are established risk factors for poor cancer prognosis. However, their associations with cancer incidence remain unclear. We investigated these associations using UK Bio...
Cancer epidemiologyEpidemiology
10.1038/S43856-026-01429-5
ISSN:2730-664X
Accelerated biological aging and risk of depression and anxiety: evidence from 424,299 UK Biobank participants
Gao Xu•Geng Tong•Jiang Meijie•Huang Ninghao•Zheng Yinan等 7 人
Nature Communications
2023
•2023/4/20
•Vol.14 No.1 p.1-12
Theory predicts that biological processes of aging may contribute to poor mental health in late life. To test this hypothesis, we evaluated prospective associations between biological age and incident depression and anxiety in 424,299 UK Biobank participants. We measured biological age from clinical...
AnxietyDepressionEpidemiologyPredictive markers
10.1038/S41467-023-38013-7
ISSN:2041-1723
Large uncertainty in individual polygenic risk score estimation impacts PRS-based risk stratification
Ding Yi•Hou Kangcheng•Burch Kathryn S.•Lapinska Sandra•Privé Florian等 8 人
Nature Genetics
2021
•2021/12/20
•00 p.1-10
Although the cohort-level accuracy of polygenic risk scores (PRSs)—estimates of genetic value at the individual level—has been widely assessed, uncertainty in PRSs remains underexplored. In the present study, we show that Bayesian PRS methods can estimate the variance of an individual’s PRS and can ...
Computational biology and bioinformaticsGenomics
10.1038/S41588-021-00961-5
ISSN:1061-4036
Allelic effects on KLHL17 expression underlie a pancreatic cancer genome-wide association signal at chr1p36.33
Katelyn E. Connelly•Katherine Hullin•Ehssan Abdolalizadeh•Jun Zhong•Daina Eiser等 17 人
Nature Communications
2025
•2025/4/30
•Vol.16 No.1 p.1-18
Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the U.S. Both rare and common germline variants contribute to PDAC risk. Here, we fine-map and functionally characterize a common PDAC risk signal at chr1p36.33 (tagged by rs13303010) identified through a ...
Cancer geneticsGene regulationGenetic variation
10.1038/S41467-025-59109-2
ISSN:2041-1723
A network correspondence toolbox for quantitative evaluation of novel neuroimaging results
Ru Kong•R. Nathan Spreng•Aihuiping Xue•Richard F. Betzel•Jessica R. Cohen等 22 人
Nature Communications
2025
•2025/3/25
•Vol.16 No.1 p.1-16
The brain can be decomposed into large-scale functional networks, but the specific spatial topographies of these networks and the names used to describe them vary across studies. Such discordance has hampered interpretation and convergence of research findings across the field. We have developed the...
Cognitive neuroscienceNeural circuits
10.1038/S41467-025-58176-9
ISSN:2041-1723
Sequencing in over 50,000 cases identifies coding and structural variation underlying atrial fibrillation risk
Seung Hoan Choi•Sean J. Jurgens•Ling Xiao•Matthew C. Hill•Christopher M. Haggerty等 103 人
Nature Genetics
2025
•2025/3/6
•Vol.57 No.3 p.548-562
Atrial fibrillation (AF) is a prevalent and morbid abnormality of the heart rhythm with a strong genetic component. Here, we meta-analyzed genome and exome sequencing data from 36 studies that included 52,416 AF cases and 277,762 controls. In burden tests of rare coding variation, we identified nove...
Atrial fibrillationCardiomyopathiesDNA sequencingGenetic association studyGenomics
10.1038/S41588-025-02074-9
ISSN:1061-4036
Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease
Jonggeol Jeffrey Kim•Dan Vitale•Diego Véliz Otani•Michelle Mulan Lian•Karl Heilbron等 18 人
Nature Genetics
2023
•2023/12/28
•00 p.1-10
Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,...
GenomicsParkinson's disease
10.1038/S41588-023-01584-8
ISSN:1061-4036
Rare coding variants in CHRNB3 associate with reduced daily cigarette smoking across ancestries
Veera M. Rajagopal•Andrey Ziyatdinov•Tyler Joseph•Ariane Ayer•Mohsin Ahmed等 27 人
Nature Communications
2026
•2026/2/24
•Vol.17 No.1 p.16540
Rare coding variants that alter protein function and confer beneficial health effects can suggest potential drug targets. CHRNB3 encodes the β3 subunit of nicotinic acetylcholine receptors that bind nicotine and mediate its action in the brain. Here we report an exome-wide association study of numbe...
Behavioural geneticsDNA sequencingGenome-wide association studies
10.1038/S41467-026-68825-2
ISSN:2041-1723
Common genetic associations between age-related diseases
Handan Melike Dönertaş•Daniel K. Fabian•Matías Fuentealba•Linda Partridge•Janet M. Thornton
Nature Aging
2021
•2021/4/8
•Vol.1 No.4 p.400-412
Age is a common risk factor in many diseases, but the molecular basis for this relationship is elusive. In this study we identified four disease clusters from 116 diseases in UK Biobank data, defined by their age-of-onset profiles, and found that diseases with the same onset profile are genetically ...
AgeingComputational biology and bioinformaticsDiseasesGenomics
10.1038/S43587-021-00051-5
ISSN:2662-8465
Mendelian randomization reveals causal effects of kidney function on various biochemical parameters
Park Sehoon•Lee Soojin•Kim Yaerim•Cho Semin•Huh Hyeok等 14 人
Communications Biology
2022
•2022/7/18
•Vol.5 No.1 p.1-8
The kidney is a vital organ with diverse biological effects and the burden of kidney function impairment is increasing in modern medicine. As the effects from kidney function on diverse biochemical parameters are yet fully understood, additional investigation to reveal the causal effects is warrante...
Diagnostic markersNephrology
10.1038/S42003-022-03659-4
ISSN:2399-3642
Improved heritability partitioning and enrichment analyses using summary statistics with graphREML
Hui Li•Tushar Kamath•Rahul Mazumder•Xihong Lin•Luke Jen O’Connor
Nature Genetics
2026
•2026/7/1
•00 p.1-10
Heritability enrichment analysis using data from genome-wide association studies is often used to understand the functional basis of genetic architecture. Stratified linkage disequilibrium score regression (S-LDSC) is a widely used method-of-moments estimator for heritability enrichment, but S-LDSC ...
Computational biology and bioinformaticsGenetics
10.1038/S41588-026-02649-0
ISSN:1061-4036
Identifying disease-critical cell types and cellular processes by integrating single-cell RNA-sequencing and human genetics
Jagadeesh Karthik A.•Dey Kushal K.•Montoro Daniel T.•Mohan Rahul•Gazal Steven等 9 人
Nature Genetics
2022
•2022/9/29
•Vol.54 No.10 p.1479-1492
Genome-wide association studies provide a powerful means of identifying loci and genes contributing to disease, but in many cases, the related cell types/states through which genes confer disease risk remain unknown. Deciphering such relationships is important for identifying pathogenic processes an...
DiseasesGene expressionGenome-wide association studiesPsychiatric disordersTranscriptomics
10.1038/S41588-022-01187-9
ISSN:1061-4036
Association of gout with brain reserve and vulnerability to neurodegenerative disease
Anya Topiwala•Kulveer Mankia•Steven Bell•Alastair Webb•Klaus P. Ebmeier等 12 人
Nature Communications
2023
•2023/5/18
•Vol.14 No.1 p.1-9
Studies of neurodegenerative disease risk in gout are contradictory. Relationships with neuroimaging markers of brain structure, which may offer insights, are uncertain. Here we investigated associations between gout, brain structure, and neurodegenerative disease incidence. Gout patients had smalle...
DementiaGout
10.1038/S41467-023-38602-6
ISSN:2041-1723
A generalized linear mixed model association tool for biobank-scale data
Jiang Longda•Zheng Zhili•Fang Hailing•Yang Jian
Nature Genetics
2021
•2021/11/4
•Vol.53 No.11 p.1616-1621
Compared with linear mixed model-based genome-wide association (GWA) methods, generalized linear mixed model (GLMM)-based methods have better statistical properties when applied to binary traits but are computationally much slower. In the present study, leveraging efficient sparse matrix-based algor...
Genome-wide association studiesSoftware
10.1038/S41588-021-00954-4
ISSN:1061-4036
High-definition likelihood inference of genetic correlations across human complex traits
Zheng Ning•Yudi Pawitan•Xia Shen
Nature Genetics
2020
•2020/6/29
•Vol.52 No.8 p.859-864
Genetic correlation is a central parameter for understanding shared genetic architecture between complex traits. By using summary statistics from genome-wide association studies (GWAS), linkage disequilibrium score regression (LDSC) was developed for unbiased estimation of genetic correlations. Alth...
Genome-wide association studiesSoftware
10.1038/S41588-020-0653-Y
ISSN:1061-4036
Genetic prediction of male pattern baldness based on large independent datasets
Chen Yan•Hysi Pirro•Maj Carlo•Heilmann-Heimbach Stefanie•Spector Timothy D.等 7 人
European Journal Of Human Genetics
2022
•2022/11/7
•Vol.31 No.3 p.321-328
Genetic prediction of male pattern baldness (MPB) is important in science and society. Previous genetic MPB prediction models were limited by sparse marker coverage, small sample size, and/or data dependency in the different analytical steps. Here, we present novel models for genetic prediction of M...
Genetic markersGenetics
10.1038/S41431-022-01201-Y
ISSN:1018-4813
Causal associations between cardiorespiratory fitness and type 2 diabetes
Lina Cai•Tomas Gonzales•Eleanor Wheeler•Nicola D. Kerrison•Felix R. Day等 9 人
Nature Communications
2023
•2023/7/3
•Vol.14 No.1 p.1-13
Higher cardiorespiratory fitness is associated with lower risk of type 2 diabetes. However, the causality of this relationship and the biological mechanisms that underlie it are unclear. Here, we examine genetic determinants of cardiorespiratory fitness in 450k European-ancestry individuals in UK Bi...
EpidemiologyGenetics researchRisk factorsType 2 diabetes
10.1038/S41467-023-38234-W
ISSN:2041-1723
Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults
Edith Hofer•Gennady V. Roshchupkin•Hieab H. H. Adams•Maria J. Knol•Honghuang Lin等 99 人
Nature Communications
2020
•2020/9/22
•Vol.11 No.1 p.1-16
Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined region...
Genetics of the nervous systemGenome-wide association studiesNeurology
10.1038/S41467-020-18367-Y
ISSN:2041-1723
A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine
Yanjun Guo•Pamela M. Rist•Iyas Daghlas•Franco Giulianini•Tobias Kurth等 6 人
Nature Communications
2020
•2020/7/6
•Vol.11 No.1 p.1-11
Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of...
Genome-wide association studiesHypertensionMigraine
10.1038/S41467-020-17002-0
ISSN:2041-1723
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
Pradeep Natarajan•Akhil Pampana•Sarah E. Graham•Sanni E. Ruotsalainen•James A. Perry等 101 人
Nature Communications
2021
•2021/4/12
•Vol.12 No.1 p.1-14
Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of...
Cardiovascular geneticsGenome-wide association studies
10.1038/S41467-021-22339-1
ISSN:2041-1723
Proteomic signatures of healthy dietary patterns are associated with lower risks of major chronic diseases and mortality
Kai Zhu•Rui Li•Pang Yao•Hancheng Yu•An Pan等 9 人
Nature Food
2024
•2024/9/27
•00 p.1-11
Healthy dietary patterns have been linked to a decreased risk of chronic diseases. However, it remains uncertain whether proteomic signatures can reflect proteome response to healthy diet patterns, and whether these proteomic signatures are associated with health outcomes. Using data from the UK Bio...
DiseasesEpidemiologyNutritionRisk factors
10.1038/S43016-024-01059-X
ISSN:2662-1355
Genomic architecture and prediction of censored time-to-event phenotypes with a Bayesian genome-wide analysis
Sven E. Ojavee•Athanasios Kousathanas•Daniel Trejo Banos•Etienne J. Orliac•Marion Patxot等 10 人
Nature Communications
2021
•2021/4/20
•Vol.12 No.1 p.1-17
While recent advancements in computation and modelling have improved the analysis of complex traits, our understanding of the genetic basis of the time at symptom onset remains limited. Here, we develop a Bayesian approach (BayesW) that provides probabilistic inference of the genetic architecture of...
Genome-wide association studiesStatistical methodsStatistics
10.1038/S41467-021-22538-W
ISSN:2041-1723
Adherence to the EAT-Lancet diet and incident depression and anxiety
Xujia Lu•Luying Wu•Liping Shao•Yulong Fan•Yalong Pei等 8 人
Nature Communications
2024
•2024/7/3
•Vol.15 No.1 p.1-11
High-quality diets have been increasingly acknowledged as a promising candidate to counter the growing prevalence of mental health disorders. This study aims to investigate the prospective associations of adhering to the EAT-Lancet reference diet with incident depression, anxiety and their co-occurr...
AnxietyDepressionEpidemiologyNutrition
10.1038/S41467-024-49653-8
ISSN:2041-1723
Dissecting task-based fMRI activity using normative modelling: an application to the Emotional Face Matching Task
Hannah S. Savage•Peter C. R. Mulders•Philip F. P. van Eijndhoven•Jasper van Oort•Indira Tendolkar等 8 人
Communications Biology
2024
•2024/7/20
•Vol.7 No.1 p.1-14
Functional neuroimaging has contributed substantially to understanding brain function but is dominated by group analyses that index only a fraction of the variation in these data. It is increasingly clear that parsing the underlying heterogeneity is crucial to understand individual differences and t...
NeurosciencePsychology
10.1038/S42003-024-06573-Z
ISSN:2399-3642
Fine-mapping a genome-wide meta-analysis of 98,374 migraine cases identifies 181 sets of candidate causal variants
Heidi Hautakangas•Joonas Kartau•Aarno Palotie•Matti Pirinen
Nature Communications
2026
•2026/1/12
•Vol.17 No.1 p.3550
Migraine is a highly prevalent neurovascular disorder for which genome-wide association studies (GWAS) have identified over one hundred risk loci, yet the causal variants and genes remain mostly unknown. Here, we meta-analyze three migraine GWAS including 98,374 cases and 869,160 controls and identi...
GeneticsGenome-wide association studiesMigraine
10.1038/S41467-025-64880-3
ISSN:2041-1723
Germline genetic scores associated with cancer gene expression and immune responses across multiple cancer types
Soojin Cha•Injeong Shim•Sang-Hyuk Jung•Beomsu Kim•Soyeon Kim等 11 人
Communications Medicine
2025
•2025/7/1
•Vol.5 No.1 p.1-9
Cancer is a polygenic disease that involves the dysregulation of multiple biological events, including aberrant cell proliferation and evasion of immune responses, which collectively contribute to cancer development and progression. Although the polygenic risk score (PRS) has enabled assessment of t...
Cancer epidemiologyCancer genetics
10.1038/S43856-025-00958-9
ISSN:2730-664X
Association of smoking and polygenic risk with the incidence of lung cancer: a prospective cohort study
Zhang Peidong•Chen Pei-Liang•Li Zhi-Hao•Zhang Ao•Zhang Xi-Ru等 8 人
British Journal Of Cancer
2022
•2022/2/22
•00 p.1-10
Genetic variation increases the risk of lung cancer, but the extent to which smoking amplifies this effect remains unknown. Therefore, we aimed to investigate the risk of lung cancer in people with different genetic risks and smoking habits. This prospective cohort study included 345,794 European an...
Lung cancerRisk factors
10.1038/S41416-022-01736-3
ISSN:0007-0920
Characterizing aging-related genetic and physiological determinants of spinal curvature
Frances M. Wang•J. Graham Ruby•Anurag Sethi•Matthew A. Veras•Natalie Telis等 6 人
Communications Medicine
2025
•2025/7/12
•Vol.5 No.1 p.1-14
Increased spinal curvature is one of the most recognizable aging traits in the human population. However, despite high prevalence, the etiology of this condition remains poorly understood. To gain better insight into the physiological, biochemical, and genetic risk factors involved, we developed a n...
EpidemiologyMedical geneticsMusculoskeletal system
10.1038/S43856-025-01003-5
ISSN:2730-664X
Temporal relationship between hepatic steatosis and blood pressure elevation and the mediation effect in the development of cardiovascular disease
Yifan Hu•Wenge Tang•Yujie Liu•Ning Zhang•Xingren Zhu等 14 人
Hypertension Research
2024
•2024/5/17
•00 p.1-11
The temporal relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension remains highly controversial, with ongoing debates on whether NAFLD induces hypertension or vice versa. We employed cross-lagged panel models to investigate the temporal relationship between hepatic steatosi...
Medicine/Public Health, generalInternal MedicinePublic HealthGeriatrics/GerontologyObstetrics/Perinatology/MidwiferyHealth Promotion and Disease Prevention
10.1038/S41440-024-01708-5
ISSN:0916-9636
Air pollution exposure modes, smoking and genetic risk with chronic respiratory diseases: a prospective study
Ting Wang•Linfang Lyu•Ru Yuan•Lei Lei•Fanqing Meng等 7 人
Npj Primary Care Respiratory Medicine
2025
•2025/12/5
•Vol.36 No.1 p.60
Previous studies often focused on single pollutant source, failing to replicate real-world exposure scenarios for chronic respiratory disease (CRD) risk. We aimed to explore the mixed exposure patterns of CRD risk factors and investigate interactions with smoking and genetic risk. We identified air ...
AsthmaChronic obstructive pulmonary diseaseDisease preventionEpidemiologyGenetics researchPublic health
10.1038/S41533-025-00469-Z
ISSN:2055-1010
Plasma proteomic signature of the human menstrual cycle
Iben Riishede•Line Rode•Pia Rengtved Lundegaard•Søren Albertsen Rand•Lars Dyrskjøt等 10 人
Nature Medicine
2026
•2026/4/13
•00 p.1-8
The menstrual cycle is one of the most fundamental biological rhythms in human physiology, yet its systemic molecular changes remain poorly understood. Here we show that the menstrual cycle is accompanied by widespread changes in the circulating proteome. By profiling nearly 3,000 plasma proteins in...
Endocrine reproductive disordersProteomics
10.1038/S41591-026-04326-5
ISSN:1078-8956
Association between mental health and MASLD molecular insights through metabolomics
Dashuai Yang•Nan Zhao•Wei Zhang•Shouxin Peng•Xian Qin等 6 人
Communications Medicine
2025
•2025/12/27
0Mental health disorders and metabolic dysfunction-associated steatotic liver disease (MASLD) represent substantial global public health challenges. The precise relationship between mental health parameters and MASLD development remains poorly characterized. Using data from the UK Biobank cohort, we ...
Diagnostic markersMetabolic disorders
10.1038/S43856-025-01317-4
ISSN:2730-664X
Leveraging longitudinal data to boost statistical power for gene–environment interaction analysis
He Xu•Yuzhuo Ma•Yufei Liu•Yin Li•Lin Wan等 10 人
Nature Computational Science
2026
•2026/6/16
•00 p.1-13
Gene–environment interaction (G×E) analyses play a crucial role in advancing genetic discovery, addressing missing heritability, and facilitating precision medicine. However, existing G×E methods are mostly designed for cross-sectional data, limiting the utility of longitudinal data. Here we propose...
Computational modelsGenetic association studyGenome-wide association studies
10.1038/S43588-026-01002-Z
ISSN:2662-8457
Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits
Evangelos Evangelou•Helen R. Warren•David Mosen-Ansorena•Borbala Mifsud•Raha Pazoki等 280 人
Nature Genetics
2018
•2018/9/17
•Vol.50 No.10 p.1412-1425
High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressu...
Cardiovascular diseasesGenome informaticsGenome-wide association studies
10.1038/S41588-018-0205-X
ISSN:1061-4036
Whole-exome sequencing study identifies rare variants and genes associated with intraocular pressure and glaucoma
Gao Xiaoyi Raymond•Chiariglione Marion•Arch Alexander J.
Nature Communications
2022
•2022/11/30
•Vol.13 No.1 p.1-10
Elevated intraocular pressure (IOP) is a major risk factor for glaucoma, the leading cause of irreversible blindness worldwide. IOP is also the only modifiable risk factor for glaucoma. Previous genome-wide association studies have established the contribution of common genetic variants to IOP. The ...
Eye diseasesGenetic association studyRare variants
10.1038/S41467-022-35188-3
ISSN:2041-1723
Conditional transcriptome-wide association study for fine-mapping candidate causal genes
Lu Liu•Ran Yan•Ping Guo•Jiadong Ji•Weiming Gong等 8 人
Nature Genetics
2024
•2024/1/26
•00 p.1-9
Transcriptome-wide association studies (TWASs) aim to integrate genome-wide association studies with expression-mapping studies to identify genes with genetically predicted expression (GReX) associated with a complex trait. In the present report, we develop a method, GIFT (gene-based integrative fin...
Computational biology and bioinformaticsGene expressionGenome-wide association studiesStatistics
10.1038/S41588-023-01645-Y
ISSN:1061-4036
Brain insulin receptor gene network shapes risk for metabolic disease after early-life stress in women
Angela Marcela Jaramillo-Ospina•Guillaume Elgbeili•Sachin Patel•Irina Pokhvisneva•Patricia Pelufo Silveira
Communications Biology
2025
•2025/9/26
•Vol.8 No.1 p.1-14
Stress happening during critical periods of development shapes individual physiology and increases the risk for obesity, inflammatory, and metabolic disturbances throughout life. However, there are individual differences and not everyone exposed to stress or adversity early during development develo...
Gene expressionRisk factors
10.1038/S42003-025-08750-0
ISSN:2399-3642
Genetic regulation across germline and somatic variation on the Y chromosome contributes to type 2 diabetes
Go Sato•Yuji Yamamoto•Kyuto Sonehara•Ryunosuke Saiki•Takafumi Ojima等 64 人
Nature Medicine
2026
•2026/2/23
•Vol.32 No.3 p.894-905
Our understanding of the biological role of the Y chromosome remains limited. Here, we systematically profile germline Y haplogroups and somatic loss of the Y chromosome (LOY) in 122,683 East Asian males from BioBank Japan and 181,472 European males from the UK Biobank. A phenome-wide scan uncovers ...
Genetic association studyType 2 diabetes
10.1038/S41591-026-04213-Z
ISSN:1078-8956
Association between genetically predicted leisure and social activities and cardiovascular disease and other health outcomes
Soyeon Kim•Hyunwoong Ko•Woojae Myung•Joohyun Yoon•Kiwon Kim等 14 人
Nature Cardiovascular Research
2025
•2025/1/2
•00 p.1-11
Participation in leisure and social activities (LSA) is associated with better health outcomes and lower mortality1–3. Previous observational studies demonstrated a relationship between engagement in LSA and both mental and physical health4,5. Although several studies6 examined the association betwe...
Clinical epigeneticsDevelopment studiesGenome-wide association studiesMolecular medicine
10.1038/S44161-024-00581-2
ISSN:2731-0590
Liability threshold model-based disease risk prediction based on electronic health record phenotypes
Cue Hyunkyu Lee•Atlas Khan•Chen Wang•Chunhua Weng•Joseph D. Buxbaum等 7 人
Nature Genetics
2025
•2025/11/3
•Vol.57 No.11 p.2872-2881
Electronic health records have been increasingly adopted as useful resources for genomic research. However, case–control labeling of clinical data from electronic health records is challenging and most studies utilize phenotype codes to define case/control labels, resulting in suboptimal downstream ...
Genetics researchGenome-wide association studies
10.1038/S41588-025-02370-4
ISSN:1061-4036
Genome-wide association study of MRI markers of cerebral small vessel disease in 42,310 participants
Elodie Persyn•Ken B. Hanscombe•Joanna M. M. Howson•Cathryn M. Lewis•Matthew Traylor等 6 人
Nature Communications
2020
•2020/5/1
•Vol.11 No.1 p.1-12
Cerebral small vessel disease is a major cause of stroke and dementia, but its genetic basis is incompletely understood. We perform a genetic study of three MRI markers of the disease in UK Biobank imaging data and other sources: white matter hyperintensities (N = 42,310), fractional anisotropy (N =...
Cerebrovascular disordersGenetics of the nervous systemGenome-wide association studies
10.1038/S41467-020-15932-3
ISSN:2041-1723
Polygenic risk score, healthy lifestyles, and risk of incident depression
Zhi Cao•Hongxi Yang•Yixuan Ye•Yuan Zhang•Shu Li等 7 人
Translational Psychiatry
2021
•2021/3/29
•Vol.11 No.1 p.1-9
Genetic factors increase the risk of depression, but the extent to which this can be offset by modifiable lifestyle factors is unknown. We investigated whether a combination of healthy lifestyles is associated with lower risk of depression regardless of genetic risk. Data were obtained from the UK B...
Clinical geneticsDepression
10.1038/S41398-021-01306-W
ISSN:2158-3188
The genetic architecture of human brainstem structures and their involvement in common brain disorders
Torbjørn Elvsåshagen•Shahram Bahrami•Dennis van der Meer•Ingrid Agartz•Dag Alnæs等 76 人
Nature Communications
2020
•2020/8/11
•Vol.11 No.1 p.1-14
Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first link...
BrainDiseases of the nervous systemGenetics of the nervous systemGenome-wide association studies
10.1038/S41467-020-17376-1
ISSN:2041-1723
Analysis of rare Parkinson’s disease variants in millions of people
Vanessa Pitz•Mary B. Makarious•Sara Bandres-Ciga•Hirotaka Iwaki•Andrew B. Singleton等 8 人
Npj Parkinson's Disease
2024
•2024/1/8
•Vol.10 No.1 p.1-10
Although many rare variants have been reportedly associated with Parkinson’s disease (PD), many have not been replicated or have failed to replicate. Here, we conduct a large-scale replication of rare PD variants. We assessed a total of 27,590 PD cases, 6701 PD proxies, and 3,106,080 controls from t...
Parkinson's diseaseRisk factors
10.1038/S41531-023-00608-8
ISSN:2373-8057
A robust cis-Mendelian randomization method with application to drug target discovery
Zhaotong Lin•Wei Pan
Nature Communications
2024
•2024/7/18
•Vol.15 No.1 p.1-14
Mendelian randomization (MR) uses genetic variants as instrumental variables (IVs) to investigate causal relationships between traits. Unlike conventional MR, cis-MR focuses on a single genomic region using only cis-SNPs. For example, using cis-pQTLs for a protein as exposure for a disease opens a c...
Cardiovascular geneticsTarget identification
10.1038/S41467-024-50385-Y
ISSN:2041-1723
Association of habitual glucosamine use with risk of microvascular complications among individuals with type 2 diabetes: a prospective cohort study in UK biobank
Zi-Jian Cheng•Yu-feng Luo•Qing-yun Zhu•Yan-fei Wang•Wen-yan Ren等 10 人
Nutrition & Diabetes
2025
•2025/4/1
•Vol.15 No.1 p.120
Glucosamine is a widely used supplement for treating osteoarthritis and joint pain. New evidence suggests a potential association between glucosamine and type 2 diabetes, inflammation and cardiometabolic risk. We aimed to prospectively evaluate the association of habitual glucosamine use with risk o...
Diabetes complicationsNutritional supplementsType 2 diabetes
10.1038/S41387-025-00369-8
ISSN:2044-4052
Studying rare variant polygenic risk scores using whole exome sequencing and imputed genotype data
Ji-One Kang•Shin Young Kwon•Hae-Un Jung•Hyein Jung•Ji Eun Lim等 6 人
Communications Biology
2025
•2025/11/24
0Rare variant polygenic scores (rvPRS) are developed to improve phenotype prediction, yet a standardized construction protocol remains unavailable. We aim to establish an optimal rvPRS protocol using whole exome sequencing (WES) and imputed genotype (IMP) data from 502,369 UK Biobank participants and...
Genetics researchStatistical methods
10.1038/S42003-025-09215-0
ISSN:2399-3642
Identity-by-descent detection across 487,409 British samples reveals fine scale population structure and ultra-rare variant associations
Juba Nait Saada•Georgios Kalantzis•Derek Shyr•Fergus Cooper•Martin Robinson等 7 人
Nature Communications
2020
•2020/11/30
•Vol.11 No.1 p.1-15
Detection of Identical-By-Descent (IBD) segments provides a fundamental measure of genetic relatedness and plays a key role in a wide range of analyses. We develop FastSMC, an IBD detection algorithm that combines a fast heuristic search with accurate coalescent-based likelihood calculations. FastSM...
Genome-wide association studiesHaplotypesHeritable quantitative traitPopulation genetics
10.1038/S41467-020-19588-X
ISSN:2041-1723
Social determinants of health, accelerated biological aging, and long-term health outcomes
Jiang Li•Jie Li•Xiaoqin Xu•Wenqi Shen•Ying Sun等 11 人
Nature Communications
2025
•2025/12/24
0Social determinants of health (SDHs) are the primary drivers of health inequalities, but whether biological aging plays a role in linking SDHs to health outcomes remains unclear. Here we utilize detailed information on social determinants across five domains, clinical parameters and electronic healt...
DiseasesHealth policy
10.1038/S41467-025-67622-7
ISSN:2041-1723
Genetic mapping and evolutionary analysis of human-expanded cognitive networks
Yongbin Wei•Siemon C. de Lange•Lianne H. Scholtens•Kyoko Watanabe•Dirk Jan Ardesch等 12 人
Nature Communications
2019
•2019/10/24
•Vol.10 No.1 p.1-11
Cognitive brain networks such as the default-mode network (DMN), frontoparietal network, and salience network, are key functional networks of the human brain. Here we show that the rapid evolutionary cortical expansion of cognitive networks in the human brain, and most pronounced the DMN, runs paral...
Cognitive neuroscienceEvolutionary geneticsGenetics of the nervous systemNeural circuits
10.1038/S41467-019-12764-8
ISSN:2041-1723
Disease trajectories and mortality among individuals diagnosed with depression: a community-based cohort study in UK Biobank
Xin Han•Can Hou•Huazhen Yang•Wenwen Chen•Zhiye Ying等 14 人
Molecular Psychiatry
2021
•2021/5/25
•00 p.1-11
Patients with depression are at increased risk for a range of comorbid diseases, with, however, unclear explanations. In this large community-based cohort study of the UK Biobank, 24,130 patients diagnosed with depression were compared to 120,366 matched individuals without such a diagnosis. Follow-...
DepressionPsychology
10.1038/S41380-021-01170-6
ISSN:1359-4184
Accelerated biological aging elevates the risk of cardiometabolic multimorbidity and mortality
Meijie Jiang•Sifan Tian•Shuzhen Liu•Yuting Wang•Xinbiao Guo等 10 人
Nature Cardiovascular Research
2024
•2024/3/1
•00 p.1-11
Associations of biological aging with the development and mortality of cardiometabolic multimorbidity (CMM) remain unclear. Here we conducted a multistate analysis in 341,159 adults of the UK Biobank. CMM was defined as the coexistence of two or three cardiometabolic diseases (CMDs), including type ...
Cardiovascular diseasesDisease preventionEndocrine system and metabolic diseases
10.1038/S44161-024-00438-8
ISSN:2731-0590
SPAGRM: effectively controlling for sample relatedness in large-scale genome-wide association studies of longitudinal traits
He Xu•Yuzhuo Ma•Lin-lin Xu•Yin Li•Yufei Liu等 12 人
Nature Communications
2025
•2025/2/6
•Vol.16 No.1 p.1-19
Sample relatedness is a major confounder in genome-wide association studies (GWAS), potentially leading to inflated type I error rates if not appropriately controlled. A common strategy is to incorporate a random effect related to genetic relatedness matrix (GRM) into regression models. However, thi...
Genome-wide association studiesRare variants
10.1038/S41467-025-56669-1
ISSN:2041-1723
A foundation model for generalizable disease detection from retinal images
Yukun Zhou•Mark A. Chia•Siegfried K. Wagner•Murat S. Ayhan•Dominic J. Williamson等 17 人
Nature
2023
•2023/9/13
•00 p.1-8
Medical artificial intelligence (AI) offers great potential for recognizing signs of health conditions in retinal images and expediting the diagnosis of eye diseases and systemic disorders1. However, the development of AI models requires substantial annotation and models are usually task-specific wi...
Cardiovascular diseasesMedical imagingPrognosisRetinal diseasesTranslational research
10.1038/S41586-023-06555-X
ISSN:0028-0836
GenNet framework: interpretable deep learning for predicting phenotypes from genetic data
van Hilten Arno•Kushner Steven A.•Kayser Manfred•Arfan Ikram M.•Adams Hieab H. H.等 8 人
Communications Biology
2021
•2021/9/17
•Vol.4 No.1 p.1-9
Applying deep learning in population genomics is challenging because of computational issues and lack of interpretable models. Here, we propose GenNet, a novel open-source deep learning framework for predicting phenotypes from genetic variants. In this framework, interpretable and memory-efficient n...
EpidemiologyMachine learningPopulation geneticsSoftware
10.1038/S42003-021-02622-Z
ISSN:2399-3642
Monogenic and polygenic inheritance become instruments for clonal selection
Po-Ru Loh•Giulio Genovese•Steven A. McCarroll
Nature
2020
•2020/6/24
•Vol.584 No.7819 p.136-141
Clonally expanded blood cells that contain somatic mutations (clonal haematopoiesis) are commonly acquired with age and increase the risk of blood cancer1–9. The blood clones identified so far contain diverse large-scale mosaic chromosomal alterations (deletions, duplications and copy-neutral loss o...
Genome-wide association studiesMutation
10.1038/S41586-020-2430-6
ISSN:0028-0836
Polygenic risk and rare variant gene clustering enhance cancer risk stratification for breast and prostate cancers
Joon Ho Kang•Youngkee Lee•Dong Jun Kim•Ji-Woong Kim•Myeong Jae Cheon等 6 人
Communications Biology
2024
•2024/10/9
•Vol.7 No.1 p.1-10
Polygenic risk score (PRS) and rare monogenic variant screening are valuable tools for predicting cancer risk and identifying individuals at high risk. Integrating both common and rare genetic variants is crucial for accurate risk assessment. However, estimating the impacts of rare variants on cance...
Computational biology and bioinformaticsRisk factors
10.1038/S42003-024-06995-9
ISSN:2399-3642
Identifying healthy individuals with Alzheimer’s disease neuroimaging phenotypes in the UK Biobank
Tiago Azevedo•Richard A. I. Bethlehem•David J. Whiteside•Nol Swaddiwudhipong•James B. Rowe等 7 人
Communications Medicine
2023
•2023/7/20
•Vol.3 No.1 p.1-15
Identifying prediagnostic neurodegenerative disease is a critical issue in neurodegenerative disease research, and Alzheimer’s disease (AD) in particular, to identify populations suitable for preventive and early disease-modifying trials. Evidence from genetic and other studies suggests the neurodeg...
BiomarkersNeuroscience
10.1038/S43856-023-00313-W
ISSN:2730-664X
Multiomics insight into disease trajectories of cardiometabolic diseases and cancer
Xuanwei Jiang•Guangrui Yang•Meng Chen•Nannan Feng•Lan Xu等 8 人
Nature Communications
2025
•2025/12/17
0Multimorbidity of cardiometabolic disease (CMD) and cancer is a growing but understudied global challenge in an aging world. Here, we perform multistate analysis in 429,555 UK Biobank participants to investigate transition patterns, identify multiomics signatures, and construct prediction models fro...
Cancer epidemiologyCardiovascular diseasesPredictive markers
10.1038/S41467-025-67510-0
ISSN:2041-1723
A genome-wide analysis of the shared genetic risk architecture of complex neurological and psychiatric disorders
Olav B. Smeland•Gleda Kutrolli•Shahram Bahrami•Vera Fominykh•Nadine Parker等 21 人
Nature Neuroscience
2025
•2025/11/11
•00 p.1-12
Although neurological and psychiatric disorders have historically been considered to reflect distinct pathogenic entities, recent findings suggest shared pathophysiological mechanisms. However, the extent to which these heritable disorders share genetic influences remains unclear. Here we performed ...
Genome-wide association studiesNeurological disordersPsychiatric disorders
10.1038/S41593-025-02090-2
ISSN:1097-6256
GIGYF1 loss of function is associated with clonal mosaicism and adverse metabolic health
Yajie Zhao•Stasa Stankovic•Mine Koprulu•Eleanor Wheeler•Felix R. Day等 13 人
Nature Communications
2021
•2021/7/7
•Vol.12 No.1 p.1-6
Mosaic loss of chromosome Y (LOY) in leukocytes is the most common form of clonal mosaicism, caused by dysregulation in cell-cycle and DNA damage response pathways. Previous genetic studies have focussed on identifying common variants associated with LOY, which we now extend to rarer, protein-coding...
Genome-wide association studiesGenomic instabilityType 2 diabetes
10.1038/S41467-021-24504-Y
ISSN:2041-1723
Improving genetic risk prediction across diverse population by disentangling ancestry representations
Prashnna K. Gyawali•Yann Le Guen•Xiaoxia Liu•Michael E. Belloy•Hua Tang等 7 人
Communications Biology
2023
•2023/9/22
•Vol.6 No.1 p.1-9
Risk prediction models using genetic data have seen increasing traction in genomics. However, most of the polygenic risk models were developed using data from participants with similar (mostly European) ancestry. This can lead to biases in the risk predictors resulting in poor generalization when ap...
Alzheimer's diseaseData mining
10.1038/S42003-023-05352-6
ISSN:2399-3642
Measurement characteristics and genome-wide correlates of lifetime brain atrophy estimated from a single MRI
Anna E. Fürtjes•Isabelle F. Foote•Charley Xia•Gail Davies•Joanna Moodie等 24 人
Nature Communications
2025
•2025/7/21
•Vol.16 No.1 p.1-15
As a cardinal marker of brain ageing, lifetime brain atrophy obtained from a cross-sectional magnetic resonance image promises to boost statistical power to uncover novel genetic mechanisms of neurodegeneration. By analysing five young and old adult cohorts, we perform the most definitive study on l...
Medical geneticsNeural ageing
10.1038/S41467-025-61978-6
ISSN:2041-1723
Mapping the relative accuracy of cross-ancestry prediction
Alexa S. Lupi•Ana I. Vazquez•Gustavo de los Campos
Nature Communications
2024
•2024/12/2
•Vol.15 No.1 p.1-14
The overwhelming majority of participants in genome-wide association studies (GWAS) have European (EUR) ancestry, and polygenic scores (PGS) derived from EURs often perform poorly in non-EURs. Previous studies suggest that between-ancestry differences in allele frequencies and linkage disequilibrium...
Population geneticsSoftwareStatistical methods
10.1038/S41467-024-54727-8
ISSN:2041-1723
Phenotypic but not genetically predicted heart rate variability associated with all-cause mortality
Balewgizie S. Tegegne•M. Abdullah Said•Alireza Ani•Arie M. van Roon•Sonia Shah等 10 人
Communications Biology
2023
•2023/10/6
•Vol.6 No.1 p.1-10
Low heart rate variability (HRV) has been widely reported as a predictor for increased mortality. However, the molecular mechanisms are poorly understood. Therefore, this study aimed to identify novel genetic loci associated with HRV and assess the association of phenotypic HRV and genetically ...
EpidemiologyGenetics research
10.1038/S42003-023-05376-Y
ISSN:2399-3642
Multi-organ metabolome biological age implicates cardiometabolic conditions and mortality risk
Filippos Anagnostakis•Sarah Ko•Mehrshad Saadatinia•Jingyue Wang•Christos Davatzikos等 6 人
Nature Communications
2025
•2025/5/26
•Vol.16 No.1 p.1-14
Multi-organ biological aging clocks across different organ systems have been shown to predict human disease and mortality. Here, we extend this multi-organ framework to plasma metabolomics, developing five organ-specific metabolome-based biological age gaps (MetBAGs) using 107 plasma non-derivatized...
Disease preventionGenome-wide association studiesPredictive markers
10.1038/S41467-025-59964-Z
ISSN:2041-1723
Grey and white matter microstructure is associated with polygenic risk for schizophrenia
Stauffer Eva-Maria•Bethlehem Richard A. I.•Warrier Varun•Murray Graham K.•Romero-Garcia Rafael等 7 人
Molecular Psychiatry
2021
•2021/8/30
•00 p.1-10
Recent discovery of approximately 270 common genetic variants associated with schizophrenia has enabled polygenic risk scores (PRS) to be measured in the population. We hypothesized that normal variation in PRS would be associated with magnetic resonance imaging (MRI) phenotypes of brain morphometry...
GeneticsNeuroscienceSchizophrenia
10.1038/S41380-021-01260-5
ISSN:1359-4184
Grip strength, genetic predisposition, and Incident Parkinson’s disease: a prospective cohort study in the UK Biobank
Wei Hu•Chun-Hua Zhao•Yue-Qing Huang•Bao-Peng Liu•Cun-Xian Jia
Npj Parkinson's Disease
2024
•2024/10/21
•Vol.10 No.1 p.1-8
To examine the association and modifiable risk factors between grip strength (GS) and Parkinson’s disease (PD) incidence considering genetic factors, a total of 411,648 individuals without PD at baseline from the UK Biobank were included. GS was measured by a hydraulic dynamometer. The polygenic ris...
Parkinson's diseaseRisk factors
10.1038/S41531-024-00810-2
ISSN:2373-8057
Depletion of loss-of-function germline mutations in centenarians reveals longevity genes
Kejun Ying•José P. Castro•Anastasia V. Shindyapina•Alexander Tyshkovskiy•Mahdi Moqri等 10 人
Nature Communications
2024
•2024/10/19
•Vol.15 No.1 p.1-11
While previous studies identified common genetic variants associated with longevity in centenarians, the role of the rare loss-of-function (LOF) mutation burden remains largely unexplored. Here, we investigated the burden of rare LOF mutations in Ashkenazi Jewish individuals from the Longevity Genes...
AgeingGenetic variationGenotype
10.1038/S41467-024-52967-2
ISSN:2041-1723
Underestimated risk of secondary complications in pathogenic and glucose-elevating GCK variant carriers with type 2 diabetes
Kelly M. Schiabor Barrett•Natalie Telis•Lisa M. McEwen•Evanette K. Burrows•Basil Khuder等 11 人
Communications Medicine
2024
•2024/11/20
•Vol.4 No.1 p.1-12
Natural HbA1c levels in GCK Maturity-onset diabetes of the young (GCK-MODY) patients often sit above the diagnostic threshold for type 2 diabetes (T2D). Treatments to lower HbA1c levels show reduced effectiveness in these individuals, yet in case studies to date, GCK-MODY patients often evade second...
Predictive markersRare variants
10.1038/S43856-024-00663-Z
ISSN:2730-664X
A stable and replicable neural signature of lifespan adversity in the adult brain
Nathalie E. Holz•Mariam Zabihi•Seyed Mostafa Kia•Maximillian Monninger•Pascal-M. Aggensteiner等 33 人
Nature Neuroscience
2023
•2023/8/21
•00 p.1-10
Environmental adversities constitute potent risk factors for psychiatric disorders. Evidence suggests the brain adapts to adversity, possibly in an adversity-type and region-specific manner. However, the long-term effects of adversity on brain structure and the association of individual neurobiologi...
Predictive markersStress and resilience
10.1038/S41593-023-01410-8
ISSN:1097-6256
Leveraging genetic overlap between irritability and psychiatric disorders to identify genetic variants of major psychiatric disorders
Kyeongmin Jung•Joohyun Yoon•Yeeun Ahn•Soyeon Kim•Injeong Shim等 23 人
Experimental & Molecular Medicine
2023
•2023/6/1
•00 p.1-10
Irritability is a heritable core mental trait associated with several psychiatric illnesses. However, the genomic basis of irritability is unclear. Therefore, this study aimed to 1) identify the genetic variants associated with irritability and investigate the associated biological pathways, genes, ...
Bipolar disorderDepressionGenome-wide association studiesSchizophrenia
10.1038/S12276-023-01005-0
ISSN:2092-6413
Genome-wide meta-analysis of iron status biomarkers and the effect of iron on all-cause mortality in HUNT
Moksnes Marta R.•Graham Sarah E.•Wu Kuan-Han•Hansen Ailin Falkmo•Gagliano Taliun Sarah A.等 19 人
Communications Biology
2022
•2022/6/16
•Vol.5 No.1 p.1-13
Iron is essential for many biological processes, but iron levels must be tightly regulated to avoid harmful effects of both iron deficiency and overload. Here, we perform genome-wide association studies on four iron-related biomarkers (serum iron, serum ferritin, transferrin saturation, total iron-b...
BiomarkersGenome-wide association studies
10.1038/S42003-022-03529-Z
ISSN:2399-3642
Association analyses identify 31 new risk loci for colorectal cancer susceptibility
Philip J. Law•Maria Timofeeva•Ceres Fernandez-Rozadilla•Peter Broderick•James Studd等 98 人
Nature Communications
2019
•2019/5/14
•Vol.10 No.1 p.1-15
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent r...
Cancer geneticsCancer genomicsColorectal cancerGenome-wide association studies
10.1038/S41467-019-09775-W
ISSN:2041-1723
Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
Alice Williamson•Dougall M. Norris•Xianyong Yin•K. Alaine Broadaway•Anne H. Moxley等 115 人
Nature Genetics
2023
•2023/6/8
•Vol.55 No.6 p.973-983
Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h af...
Gene expressionGenome-wide association studiesMetabolic disordersPopulation geneticsType 2 diabetes
10.1038/S41588-023-01408-9
ISSN:1061-4036
Accounting for genetic effect heterogeneity in fine-mapping and improving power to detect gene-environment interactions with SharePro
Wenmin Zhang•Robert Sladek•Yue Li•Hamed Najafabadi•Josée Dupuis
Nature Communications
2024
•2024/10/30
•Vol.15 No.1 p.1-11
Classical gene-by-environment interaction (GxE) analysis can be used to characterize genetic effect heterogeneity but has a high multiple testing burden in the context of genome-wide association studies (GWAS). We adapt a colocalization method, SharePro, to account for effect heterogeneity in fine-m...
Computational biology and bioinformaticsGenetics
10.1038/S41467-024-53818-W
ISSN:2041-1723
Proteome atlas for mechanistic discovery and risk prediction of diabetic retinopathy
Shaopeng Yang•Zhuoyao Xin•Ruilin Xiong•Ziyu Zhu•Huangdong Li等 21 人
Nature Communications
2025
•2025/10/31
•Vol.16 No.1 p.1-21
Proteomics offers an unprecedented opportunity to characterize and predict diabetic retinopathy (DR) with minimal invasiveness. Here we examine this in 10,873 individuals with (pre)diabetes from two ethnically distinct cohorts. By simultaneous profiling of ~3000 proteins, we identify 668 association...
Diabetes complicationsEpidemiologyPredictive markersPreventive medicineRisk factors
10.1038/S41467-025-64634-1
ISSN:2041-1723
GWAS-by-subtraction reveals an IOP-independent component of primary open angle glaucoma
Yu Huang•Denis Plotnikov•Huan Wang•Danli Shi•Cong Li等 14 人
Nature Communications
2024
•2024/10/17
•Vol.15 No.1 p.1-15
The etiology of primary open angle glaucoma is constituted by both intraocular pressure-dependent and intraocular pressure-independent mechanisms. However, GWASs of traits affecting primary open angle glaucoma through mechanisms independent of intraocular pressure remains limited. Here, we address t...
Genome-wide association studiesGlaucomaHereditary eye disease
10.1038/S41467-024-53331-0
ISSN:2041-1723
Association of air pollution exposure and genetic susceptibility with increased risk of thoracic aortic aneurysm and dissection
Yudiyang Ma•Jianing Wang•Linxi Tang•Feipeng Cui•Lei Zheng等 7 人
Nature Cardiovascular Research
2025
•2025/9/26
•00 p.1-12
Thoracic aortic aneurysm and dissection (TAAD) represent a serious health threat, yet the role of air pollution exposure on its development has been underexplored. Here we investigate the relationships between air pollutants and TAAD incidence. In a Cox’s proportional hazards model, hazard ratios (9...
Genetic association studyInterventional cardiology
10.1038/S44161-025-00719-W
ISSN:2731-0590
The genetic architecture of the human thalamus and its overlap with ten common brain disorders
Torbjørn Elvsåshagen•Alexey Shadrin•Oleksandr Frei•Dennis van der Meer•Shahram Bahrami等 10 人
Nature Communications
2021
•2021/5/18
•Vol.12 No.1 p.1-9
The thalamus is a vital communication hub in the center of the brain and consists of distinct nuclei critical for consciousness and higher-order cortical functions. Structural and functional thalamic alterations are involved in the pathogenesis of common brain disorders, yet the genetic architecture...
BrainDiseases of the nervous systemGenetics researchNeurological disordersPsychiatric disorders
10.1038/S41467-021-23175-Z
ISSN:2041-1723
Towards a general-purpose foundation model for functional MRI analysis
Cheng Wang•Yu Jiang•Zhihao Peng•Chenxin Li•Chang-bae Bang等 21 人
Nature Biomedical Engineering
2026
•2026/4/23
•00 p.1-12
Functional magnetic resonance imaging (fMRI) is crucial for studying brain function and diagnosing neurological disorders. However, existing analysis methods suffer from reproducibility and transferability challenges due to complex preprocessing pipelines and task-specific model designs. Here we int...
Computational scienceMagnetic resonance imaging
10.1038/S41551-026-01666-Y
ISSN:2157-846X
Green environments and cardiometabolic health: exploring incidence and progression through multi-state analysis
Linxi Tang•Dankang Li•Yudiyang Ma•Feipeng Cui•Jianing Wang等 7 人
Npj Urban Sustainability
2025
•2025/4/17
•Vol.5 No.1 p.1-8
It is unknown how greenness affects the development, progression and prognosis of cardiometabolic multimorbidity (CMM). We aimed to evaluate the role of greenness on trajectories of CMM, particularly the transitions from healthy to first cardiometabolic disease (FCMD), then to CMM and followed by de...
Environmental impactEpidemiology
10.1038/S42949-025-00201-3
ISSN:2661-8001
Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis
Pooja Middha•Rohit Thummalapalli•Michael J. Betti•Lydia Yao•Zoe Quandt等 27 人
Nature Communications
2024
•2024/3/26
•Vol.15 No.1 p.1-10
Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohn’s disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk score...
Cancer epidemiologyCancer geneticsNon-small-cell lung cancerOutcomes research
10.1038/S41467-023-44512-4
ISSN:2041-1723
Linear and non-linear proteome-wide association studies provide novel insight into venous thromboembolism
Yifan Kong•Wangxia Tang•Haonan Kang•Yunlong Guan•Si Li等 10 人
Nature Communications
2025
•2025/7/15
•Vol.16 No.1 p.1-12
Venous thromboembolism is a life-threatening vascular event with high prevalence and genetic determinants. PWAS has become a popular strategy to identify therapeutic targets of complex diseases. However, the current PWAS model only considers the linear relationship between protein and disease. Here,...
Cardiovascular diseasesDiagnostic markersHaematological diseasesPredictive markersProteome informatics
10.1038/S41467-025-61874-Z
ISSN:2041-1723
Demonstrating paths for unlocking the value of cloud genomics through cross cohort analysis
Nicole Deflaux•Margaret Sunitha Selvaraj•Henry Robert Condon•Kelsey Mayo•Sara Haidermota等 17 人
Nature Communications
2023
•2023/9/5
•Vol.14 No.1 p.1-10
Recently, large scale genomic projects such as All of Us and the UK Biobank have introduced a new research paradigm where data are stored centrally in cloud-based Trusted Research Environments (TREs). To characterize the advantages and drawbacks of different TRE attributes in facilitating cross-coho...
Data integrationGenome-wide association studiesGenomic analysis
10.1038/S41467-023-41185-X
ISSN:2041-1723
Body mass index stratification optimizes polygenic prediction of type 2 diabetes in cross-biobank analyses
Takafumi Ojima•Shinichi Namba•Ken Suzuki•Kenichi Yamamoto•Kyuto Sonehara等 12 人
Nature Genetics
2024
•2024/6/11
•Vol.56 No.6 p.1100-1109
Type 2 diabetes (T2D) shows heterogeneous body mass index (BMI) sensitivity. Here, we performed stratification based on BMI to optimize predictions for BMI-related diseases. We obtained BMI-stratified datasets using data from more than 195,000 individuals (nT2D = 55,284) from BioBank Japan (BBJ) and...
Cardiovascular diseasesGenome-wide association studiesMetabolic disordersTranslational research
10.1038/S41588-024-01782-Y
ISSN:1061-4036
Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience
Sean J. Jurgens•Joel T. Rämö•Daria R. Kramarenko•Leonoor F. J. M. Wijdeveld•Jan Haas等 58 人
Nature Genetics
2024
•2024/11/21
•00 p.1-10
Dilated cardiomyopathy (DCM) is a heart muscle disease that represents an important cause of morbidity and mortality, yet causal mechanisms remain largely elusive. Here, we perform a large-scale genome-wide association study and multitrait analysis for DCM using 9,365 cases and 946,368 controls. We ...
CardiomyopathiesGenome-wide association studiesHeart failure
10.1038/S41588-024-01975-5
ISSN:1061-4036
Decoding sexually dimorphic proteomic landscapes in the context of aging and mortality
Zhihao Jin•Bingying Du•Xuehao Jiao•Zhengsheng Gu•Tianren Wang等 10 人
Communications Medicine
2025
•2025/9/29
•Vol.5 No.1 p.1-16
Aging-associated changes are major contributors to the onset and progression of chronic diseases. Different aging clocks have been developed to assess biological aging, demonstrating their utility in predicting mortality, diagnosing disease, and evaluating the efficacy of antiaging interventions. Ho...
Predictive markers
10.1038/S43856-025-01113-0
ISSN:2730-664X
Germline variant burden in cancer genes correlates with age at diagnosis and somatic mutation burden
Tao Qing•Hussein Mohsen•Michal Marczyk•Yixuan Ye•Tess O’Meara等 11 人
Nature Communications
2020
•2020/5/15
•Vol.11 No.1 p.1-8
Cancers harbor many somatic mutations and germline variants, we hypothesized that the combined effect of germline variants that alter the structure, expression, or function of protein-coding regions of cancer-biology related genes (gHFI) determines which and how many somatic mutations (sM) must occu...
Cancer genomicsCancer prevention
10.1038/S41467-020-16293-7
ISSN:2041-1723
Whole-exome sequencing identifies protein-coding variants associated with brain iron in 29,828 individuals
Weikang Gong•Yan Fu•Bang-Sheng Wu•Jingnan Du•Liu Yang等 14 人
Nature Communications
2024
•2024/7/2
•Vol.15 No.1 p.1-13
Iron plays a fundamental role in multiple brain disorders. However, the genetic underpinnings of brain iron and its implications for these disorders are still lacking. Here, we conduct an exome-wide association analysis of brain iron, measured by quantitative susceptibility mapping technique, across...
Diseases of the nervous systemGenetic association studyGenetics of the nervous system
10.1038/S41467-024-49702-2
ISSN:2041-1723
Integration of variant annotations using deep set networks boosts rare variant association testing
Brian Clarke•Eva Holtkamp•Hakime Öztürk•Marcel Mück•Magnus Wahlberg等 13 人
Nature Genetics
2024
•2024/9/25
•00 p.1-10
Rare genetic variants can have strong effects on phenotypes, yet accounting for rare variants in genetic analyses is statistically challenging due to the limited number of allele carriers and the burden of multiple testing. While rich variant annotations promise to enable well-powered rare variant a...
Population geneticsSequence annotation
10.1038/S41588-024-01919-Z
ISSN:1061-4036
Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke
Gad Abraham•Rainer Malik•Ekaterina Yonova-Doing•Agus Salim•Tingting Wang等 10 人
Nature Communications
2019
•2019/12/20
•Vol.10 No.1 p.1-10
Recent genome-wide association studies in stroke have enabled the generation of genomic risk scores (GRS) but their predictive power has been modest compared to established stroke risk factors. Here, using a meta-scoring approach, we develop a metaGRS for ischaemic stroke (IS) and analyse this score...
Genome-wide association studiesPersonalized medicineRisk factorsStroke
10.1038/S41467-019-13848-1
ISSN:2041-1723
Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy
Natalie DeForest•Yuqi Wang•Zhiyi Zhu•Jacqueline S. Dron•Ryan Koesterer等 10 人
Nature Communications
2024
•2024/9/14
•Vol.15 No.1 p.1-17
Insulin resistance causes multiple epidemic metabolic diseases, including type 2 diabetes, cardiovascular disease, and fatty liver, but is not routinely measured in epidemiological studies. To discover novel insulin resistance genes in the general population, we conducted genome-wide association stu...
Functional genomicsGenetic markersMetabolic syndrome
10.1038/S41467-024-52105-Y
ISSN:2041-1723
Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis
Go Sato•Yuya Shirai•Shinichi Namba•Ryuya Edahiro•Kyuto Sonehara等 11 人
Nature Communications
2023
•2023/6/20
•Vol.14 No.1 p.1-11
Integrating genomic data of multiple cancers allows de novo cancer grouping and elucidating the shared genetic basis across cancers. Here, we conduct the pan-cancer and cross-population genome-wide association study (GWAS) meta-analysis and replication studies on 13 cancers including 250,015 East As...
Cancer geneticsGenome-wide association studies
10.1038/S41467-023-39136-7
ISSN:2041-1723
A cross population study of retinal aging biomarkers with longitudinal pre-training and label distribution learning
Zhen Yu•Ruiye Chen•Peng Gui•Wei Wang•Imran Razzak等 17 人
Npj Digital Medicine
2025
•2025/6/10
•Vol.8 No.1 p.1-14
Retinal age has emerged as a promising biomarker of aging, offering a non-invasive and accessible assessment tool. We developed a deep learning model to estimate retinal age with enhanced accuracy, leveraging retinal images from diverse populations. Our approach integrates self-supervised learning t...
Predictive markersRisk factors
10.1038/S41746-025-01751-7
ISSN:2398-6352
Leveraging fine-mapping and multipopulation training data to improve cross-population polygenic risk scores
Weissbrod Omer•Kanai Masahiro•Shi Huwenbo•Gazal Steven•Peyrot Wouter J.等 10 人
Nature Genetics
2022
•2022/4/7
•00 p.1-9
Polygenic risk scores suffer reduced accuracy in non-European populations, exacerbating health disparities. We propose PolyPred, a method that improves cross-population polygenic risk scores by combining two predictors: a new predictor that leverages functionally informed fine-mapping to estimate ca...
Clinical geneticsDiseases
10.1038/S41588-022-01036-9
ISSN:1061-4036
Associations of dietary folate, vitamin B6 and B12 intake with cardiovascular outcomes in 115664 participants: a large UK population-based cohort
Zhang Boya•Dong Haoyu•Xu Ying•Xu Duo•Sun Hongpeng等 6 人
European Journal Of Clinical Nutrition
2022
•2022/9/13
•Vol.77 No.3 p.299-307
The evidence of relationship between dietary intake of folate, vitamin B6 and vitamin B12 and cardiovascular diseases (CVD) in UK populations is limited. We aimed to analyze the association of dietary intake of folate, vitamin B6, and vitamin B12 with CVD events [stroke, myocardial infarction (MI)] ...
Cardiovascular diseasesDiseasesHealth careMedical research
10.1038/S41430-022-01206-2
ISSN:0954-3007
Quantification of frequency-dependent genetic architectures in 25 UK Biobank traits reveals action of negative selection
Armin P. Schoech•Daniel M. Jordan•Po-Ru Loh•Steven Gazal•Luke J. O’Connor等 10 人
Nature Communications
2019
•2019/2/15
•Vol.10 No.1 p.1-10
Understanding the role of rare variants is important in elucidating the genetic basis of human disease. Negative selection can cause rare variants to have larger per-allele effect sizes than common variants. Here, we develop a method to estimate the minor allele frequency (MAF) dependence of SNP eff...
GeneticsGenetics researchPopulation genetics
10.1038/S41467-019-08424-6
ISSN:2041-1723
Insights into DNA repeat expansions among 900,000 biobank participants
Margaux L. A. Hujoel•Robert E. Handsaker•David Tang•Nolan Kamitaki•Ronen E. Mukamel等 9 人
Nature
2026
•2026/1/7
•Vol.650 No.8103 p.920-929
Expansions and contractions of tandem DNA repeats generate genetic variation in human populations and in human tissues. Some expanded repeats cause inherited disorders and some are also somatically unstable1,2. Here we analysed DNA sequencing data from over 900,000 participants in the UK Bioban...
Genetic association studyGenomic instabilityMutation
10.1038/S41586-025-09886-Z
ISSN:0028-0836
Computation and resource efficient genome-wide association analysis for large-scale imaging studies
Zhiwen Jiang•Jason Stein•Tengfei Li•Ethan Fang•Yun Li等 7 人
Nature Communications
2026
•2026/2/28
•Vol.17 No.1 p.33130
Imaging genetics links genetic variations to brain structures and functions, but the computational challenges posed by high-dimensional imaging and genetic data are significant. In voxel-level genome-wide association studies, we introduce a Representation learning-based Voxel-level Genetic Analysis ...
Genome-wide association studiesImage processingLearning algorithms
10.1038/S41467-026-69816-Z
ISSN:2041-1723
Mediterranean diet and rheumatoid arthritis: A nine-year cohort study and systematic review with meta-analysis
Peipei Hu•Eric Kam-Pui Lee•Qian Li•Lai-Shan Tam•Samuel Yeung-Shan Wong等 7 人
European Journal Of Clinical Nutrition
2025
•2025/5/7
•00 p.1-9
Although the Mediterranean diet (MD) has beneficial effects on heart health, cognitive function, cancer, and other chronic diseases, little is known about its effect on rheumatoid arthritis (RA). This study aimed to examine the association between adherence to MD and the risk of developing rheumatoi...
EpidemiologyRisk factors
10.1038/S41430-025-01628-8
ISSN:0954-3007
Large-scale plasma proteomics uncovers novel targets linking ambient air pollution and depression
Chuyu Pan•Xin Qi•Xuena Yang•Bolun Cheng•Shiqiang Cheng等 15 人
Molecular Psychiatry
2025
•2025/3/19
•00 p.1-10
Despite the growing recognition of association between air pollution and increased risk of depression, the intricate biological mechanisms underlying it remains unclear. In this study, a total of 1463 plasma proteins were measured by the Olink Explore platform for 50,553 participants in a large pros...
BiomarkersDepression
10.1038/S41380-025-02953-X
ISSN:1359-4184
Whole-exome sequencing and burden analysis identify six novel candidate risk genes and expand the genetic landscape of Parkinson’s disease
Yu Fan•Zhen Hu•Qin-qin Yan•Jing-jin Wan•Jun Liu
Npj Parkinson's Disease
2025
•2025/12/3
•Vol.11 No.1 p.3470
Parkinson’s Disease (PD) is a complex neurodegenerative disorder with a largely undefined genetic architecture, particularly regarding the role of rare coding variants. We performed a large-scale exome-wide association study to systematically identify rare genetic risk factors for PD. We analyzed wh...
Computational biology and bioinformaticsDiseasesGeneticsNeurologyNeuroscience
10.1038/S41531-025-01195-6
ISSN:2373-8057
A genome-wide association analysis reveals new pathogenic pathways in gout
Tanya J. Major•Riku Takei•Hirotaka Matsuo•Megan P. Leask•Nicholas A. Sumpter等 98 人
Nature Genetics
2024
•2024/10/15
•00 p.1-15
Gout is a chronic disease that is caused by an innate immune response to deposited monosodium urate crystals in the setting of hyperuricemia. Here, we provide insights into the molecular mechanism of the poorly understood inflammatory component of gout from a genome-wide association study (GWAS) of ...
Genetics researchGout
10.1038/S41588-024-01921-5
ISSN:1061-4036
Subtyping Alzheimer’s disease and Parkinson’s disease using longitudinal electronic health records
Jie Lian•Zhengxian Fan•Ben Omega Petrazzini•Wei Fan•Shishir Rao等 11 人
Nature Aging
2026
•2026/2/26
•Vol.6 No.3 p.612-625
Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are clinically heterogeneous, hampering the success of nonselective treatment strategies. Here we apply a transformer-based unsupervised clustering framework to longitudinal electronic health record data from ov...
AgeingExperimental models of diseaseNeurodegenerative diseasesPredictive markers
10.1038/S43587-026-01085-3
ISSN:2662-8465
A phenome-wide association study of tandem repeat variation in 168,554 individuals from the UK Biobank
Celine A. Manigbas•Bharati Jadhav•Paras Garg•Mariya Shadrina•William Lee等 8 人
Nature Communications
2024
•2024/12/3
•Vol.15 No.1 p.1-12
Most genetic association studies focus on binary variants. To identify the effects of multi-allelic variation of tandem repeats (TRs) on human traits, we perform direct TR genotyping and phenome-wide association studies in 168,554 individuals from the UK Biobank, identifying 47 TRs showing fine-mapp...
Genetic predisposition to diseaseGenetic variationGenome-wide association studies
10.1038/S41467-024-54678-0
ISSN:2041-1723
Integrating 3D genomic and epigenomic data to enhance target gene discovery and drug repurposing in transcriptome-wide association studies
Khunsriraksakul Chachrit•McGuire Daniel•Sauteraud Renan•Chen Fang•Yang Lina等 14 人
Nature Communications
2022
•2022/6/7
•Vol.13 No.1 p.1-15
Transcriptome-wide association studies (TWAS) are popular approaches to test for association between imputed gene expression levels and traits of interest. Here, we propose an integrative method PUMICE (Prediction Using Models Informed by Chromatin conformations and Epigenomics) to integrate 3D geno...
EpigenomicsGene regulationGenome-wide association studiesTranscriptomics
10.1038/S41467-022-30956-7
ISSN:2041-1723
Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking
Weixiong He•Peter J. van der Most•Jue-Sheng Ong•Liang-Dar Hwang•Yeda Wu等 24 人
Nature Communications
2025
•2025/8/23
•Vol.16 No.1 p.1-14
Strabismus is a common pediatric eye misalignment and has complex genetic and environmental causes. Previous genome-wide association studies (GWAS) encountered difficulties in identifying strabismus risk variants due to heterogeneity and small samples. We performed large meta-analyses of 11 European...
Refractive errorsRisk factors
10.1038/S41467-025-62456-9
ISSN:2041-1723
Genetic variants associated with platelet count are predictive of human disease and physiological markers
Mikaelsdottir Evgenia•Thorleifsson Gudmar•Stefansdottir Lilja•Halldorsson Gisli•Sigurdsson Jon K.等 33 人
Communications Biology
2021
•2021/9/27
•Vol.4 No.1 p.1-13
Platelets play an important role in hemostasis and other aspects of vascular biology. We conducted a meta-analysis of platelet count GWAS using data on 536,974 Europeans and identified 577 independent associations. To search for mechanisms through which these variants affect platelets, we applied ci...
Gene expressionGenome-wide association studiesQuantitative trait
10.1038/S42003-021-02642-9
ISSN:2399-3642
Adjusting for common variant polygenic scores improves yield in rare variant association analyses
Jurgens Sean J.•Pirruccello James P.•Choi Seung Hoan•Morrill Valerie N.•Chaffin Mark等 8 人
Nature Genetics
2023
•2023/3/23
•00 p.1-5
With the emergence of large-scale sequencing data, methods for improving power in rare variant association tests are needed. Here we show that adjusting for common variant polygenic scores improves yield in gene-based rare variant association tests across 65 quantitative traits in the UK Biobank (up...
DNA sequencingGenome informaticsGenome-wide association studies
10.1038/S41588-023-01342-W
ISSN:1061-4036
Data-driven prioritization of high-risk individuals for weight loss interventions
Kamil Demircan•Julia Carrasco-Zanini•Alice Williamson•Carl Beuchel•Linsey Jackson等 15 人
Nature Medicine
2026
•2026/4/30
•00 p.1-11
New obesity medications have demonstrated efficacy in trials, but their real-world deployment is partly limited by the absence of approaches that identify individuals for treatment based on risks for obesity-related complications. Here we present a risk prediction model to guide prioritization of hi...
Predictive markersPredictive medicinePrognostic markers
10.1038/S41591-026-04353-2
ISSN:1078-8956
Genotype by sex interactions in ankylosing spondylitis
Li Zhixiu•McRae Allan F.•Wang Geng•Ellis Jonathan J.•Whyte Jessica等 8 人
Nature Genetics
2023
•2023/1/9
•Vol.55 No.1 p.14-16
Autoimmune diseasesGenome-wide association studies
10.1038/S41588-022-01250-5
ISSN:1061-4036
Coagulation factor XII haploinsufficiency is protective against venous thromboembolism in a population-scale multidimensional analysis
Amelia K. Haj•David S. Paul•Sean J. Jurgens•Harish Eswaran•Lu-Chen Weng等 21 人
Nature Communications
2025
•2025/9/1
•Vol.16 No.1 p.1-12
Coagulation factor XII has been identified as a potential drug target that could prevent thrombosis without increasing the risk of bleeding. However, human data to support the development of factor XII-directed therapeutics are lacking. To assess the role of factor XII in venous thromboembolism, we ...
Cardiovascular geneticsPopulation geneticsThromboembolism
10.1038/S41467-025-62789-5
ISSN:2041-1723
Multi-omic signatures and trajectories of cardiometabolic diseases and depression
Guangrui Yang•Xuanwei Jiang•Jingxuan Wang•Shuxiao Shi•Sujing Wang等 12 人
Nature Mental Health
2026
•2026/6/24
•00 p.1-12
Cardiometabolic diseases (CMDs) and depression frequently co-occur and substantially increase mortality risk yet their multimorbidity trajectories and underlying biological mechanisms remain unclear. Here we analyzed 467,592 UK Biobank participants without baseline CMDs or depression, utilizing mult...
DepressionPredictive markers
10.1038/S44220-026-00678-6
ISSN:2731-6076
Accelerometer-derived ‘weekend warrior’ physical activity pattern and brain health
Jiahao Min•Zhi Cao•Tingshan Duan•Yaogang Wang•Chenjie Xu
Nature Aging
2024
•2024/8/21
•00 p.1-9
Extensive evidence shows the beneficial effect of adhering to a regular physical activity (PA) pattern on brain health. However, whether the ‘weekend warrior’ pattern, characterized by concentrated moderate-to-vigorous PA (MVPA) over 1–2 days, is associated with brain health is unclear. Here, we per...
AgeingNeurological disordersPsychiatric disorders
10.1038/S43587-024-00688-Y
ISSN:2662-8465
Spatiotemporal dynamics of the human cortical functional hierarchy across the lifespan
Qiongling Li•Xinyuan Liang•Debin Zeng•Tengda Zhao•Xuhong Liao等 74 人
Nature Communications
2026
•2026/4/7
0The human cortical functional hierarchy, spanning from primary sensorimotor to transmodal association regions, represents a fundamental principle of brain organisation. Here, we show lifespan changes in the sensorimotor-association (S-A) gradient in the cortical functional hierarchy using multimodal...
Cognitive neuroscienceFunctional magnetic resonance imaging
10.1038/S41467-026-71270-W
ISSN:2041-1723
Secure and federated genome-wide association studies for biobank-scale datasets
Hyunghoon Cho•David Froelicher•Jeffrey Chen•Manaswitha Edupalli•Apostolos Pyrgelis等 8 人
Nature Genetics
2025
•2025/2/24
•00 p.1-6
Sharing data across institutions for genome-wide association studies (GWAS) would enhance the discovery of genetic variation linked to health and disease1,2. However, existing data-sharing regulations limit the scope of such collaborations3. Although cryptographic tools for secure computation promis...
Computational biology and bioinformaticsGenome-wide association studiesSoftware
10.1038/S41588-025-02109-1
ISSN:1061-4036
Symptom-level modelling unravels the shared genetic architecture of anxiety and depression
Jackson G. Thorp•Adrian I. Campos•Andrew D. Grotzinger•Zachary F. Gerring•Jiyuan An等 14 人
Nature Human Behaviour
2021
•2021/4/15
•00 p.1-11
Depression and anxiety are highly prevalent and comorbid psychiatric traits that cause considerable burden worldwide. Here we use factor analysis and genomic structural equation modelling to investigate the genetic factor structure underlying 28 items assessing depression, anxiety and neuroticism, a...
AnxietyDepressionGenome-wide association studies
10.1038/S41562-021-01094-9
ISSN:2397-3374
Polygenic risk alters the penetrance of monogenic kidney disease
Atlas Khan•Ning Shang•Jordan G. Nestor•Chunhua Weng•George Hripcsak等 8 人
Nature Communications
2023
•2023/12/14
•Vol.14 No.1 p.1-10
Chronic kidney disease (CKD) is determined by an interplay of monogenic, polygenic, and environmental risks. Autosomal dominant polycystic kidney disease (ADPKD) and COL4A-associated nephropathy (COL4A-AN) represent the most common forms of monogenic kidney diseases. These disorders have incomplete ...
Chronic kidney diseasePolycystic kidney disease
10.1038/S41467-023-43878-9
ISSN:2041-1723
GWAS of serum ALT and AST reveals an association of SLC30A10 Thr95Ile with hypermanganesemia symptoms
Ward Lucas D.•Tu Ho-Chou•Quenneville Chelsea B.•Tsour Shira•Flynn-Carroll Alexander O.等 14 人
Nature Communications
2021
•2021/7/27
•Vol.12 No.1 p.1-14
Understanding mechanisms of hepatocellular damage may lead to new treatments for liver disease, and genome-wide association studies (GWAS) of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum activities have proven useful for investigating liver biology. Here we report 100 lo...
Bile duct cancerGenome-wide association studiesHepatocytesLiver diseases
10.1038/S41467-021-24563-1
ISSN:2041-1723
Performance of different polygenic risk scores for breast cancer risk prediction: in-depth evaluations across large UK and Australian cohorts
Hamzeh M. Tanha•Matthew H. Law•Nathan Ingold•Catherine M. Olsen•Nirmala Pandeya等 10 人
European Journal Of Human Genetics
2026
•2026/1/13
•Vol.34 No.2 p.278-287
Polygenic risk scores (PGS) have the potential to support enhanced, risk-based screening for breast cancer. Previous studies for many diseases found that genome-wide PGS (GW-PGS) outperform PGS derived by applying hard GWAS significance thresholds. To support future breast cancer risk predictions, w...
Breast cancerEpidemiologyGenetics research
10.1038/S41431-025-02003-8
ISSN:1018-4813
Incorporating functional priors improves polygenic prediction accuracy in UK Biobank and 23andMe data sets
Márquez-Luna Carla•Gazal Steven•Loh Po-Ru•Kim Samuel S.•Furlotte Nicholas等 7 人
Nature Communications
2021
•2021/10/18
•Vol.12 No.1 p.1-11
Polygenic risk prediction is a widely investigated topic because of its promising clinical applications. Genetic variants in functional regions of the genome are enriched for complex trait heritability. Here, we introduce a method for polygenic prediction, LDpred-funct, that leverages trait-specific...
Disease geneticsGenome-wide association studiesGenotypeStatistical methods
10.1038/S41467-021-25171-9
ISSN:2041-1723
Investigating genetically stratified subgroups to better understand the etiology of alcohol misuse
Anaïs B. Thijssen•Danielle M. Dick•Danielle Posthuma•Jeanne E. Savage
Molecular Psychiatry
2023
•2023/7/25
•00 p.1-9
Alcohol misuse (AM) is highly prevalent and harmful, with theorized subgroups differing on internalizing and externalizing dimensions. Despite known heterogeneity, genome-wide association studies (GWAS) are usually conducted on unidimensional phenotypes. These approaches have identified important ge...
AddictionGeneticsPsychology
10.1038/S41380-023-02174-0
ISSN:1359-4184
Air pollution and dynamic transitions of preserved ratio impaired spirometry in UK Biobank
Xueyan Han•Zhaoyang Pan•Yimin Qu•Jian Guo•Hailu Zhu等 12 人
Communications Medicine
2025
•2025/11/12
0Although air pollution has been recognized as a risk factor for chronic obstructive pulmonary disease (COPD), little is known regarding the role of air pollutant exposure, specifically particulate matter (PM), in the dynamic transitions among normal spirometry (lung function), pre-COPD status, and C...
EpidemiologyMedical research
10.1038/S43856-025-01225-7
ISSN:2730-664X
Biological markers and psychosocial factors predict chronic pain conditions
Matt Fillingim•Christophe Tanguay-Sabourin•Marc Parisien•Azin Zare•Gianluca V. Guglietti等 13 人
Nature Human Behaviour
2025
•2025/5/12
•00 p.1-16
Chronic pain is a multifactorial condition presenting significant diagnostic and prognostic challenges. Biomarkers for the classification and the prediction of chronic pain are therefore critically needed. Here, in this multidataset study of over 523,000 participants, we applied machine learning to ...
Predictive markersRisk factors
10.1038/S41562-025-02156-Y
ISSN:2397-3374
Aggregative trans-eQTL analysis detects trait-specific target gene sets in whole blood
Dutta Diptavo•He Yuan•Saha Ashis•Arvanitis Marios•Battle Alexis等 6 人
Nature Communications
2022
•2022/7/26
•Vol.13 No.1 p.1-14
Large scale genetic association studies have identified many trait-associated variants and understanding the role of these variants in the downstream regulation of gene-expressions can uncover important mediating biological mechanisms. Here we propose ARCHIE, a summary statistic based sparse canonic...
Gene expressionGene regulatory networksGenetic association study
10.1038/S41467-022-31845-9
ISSN:2041-1723
Biobank-scale inference of ancestral recombination graphs enables genealogical analysis of complex traits
Zhang Brian C.•Biddanda Arjun•Gunnarsson Árni Freyr•Cooper Fergus•Palamara Pier Francesco
Nature Genetics
2023
•2023/5/1
•00 p.1-9
Genome-wide genealogies compactly represent the evolutionary history of a set of genomes and inferring them from genetic data has the potential to facilitate a wide range of analyses. We introduce a method, ARG-Needle, for accurately inferring biobank-scale genealogies from sequencing or genotyping ...
Genome-wide association studiesPopulation genetics
10.1038/S41588-023-01379-X
ISSN:1061-4036
Protein-altering variants at copy number-variable regions influence diverse human phenotypes
Margaux L. A. Hujoel•Robert E. Handsaker•Maxwell A. Sherman•Nolan Kamitaki•Alison R. Barton等 9 人
Nature Genetics
2024
•2024/3/28
•00 p.1-10
Copy number variants (CNVs) are among the largest genetic variants, yet CNVs have not been effectively ascertained in most genetic association studies. Here we ascertained protein-altering CNVs from UK Biobank whole-exome sequencing data (n = 468,570) using haplotype-informed methods capable of dete...
Genome informaticsGenome-wide association studiesGenotyping and haplotyping
10.1038/S41588-024-01684-Z
ISSN:1061-4036
Comprehensive genetic study of the insulin resistance marker TG:HDL-C in the UK Biobank
Antonino Oliveri•Ryan J Rebernick•Annapurna Kuppa•Asmita Pant•Yanhua Chen等 13 人
Nature Genetics
2024
•2024/1/10
•00 p.1-10
Insulin resistance (IR) is a well-established risk factor for metabolic disease. The ratio of triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) is a surrogate marker of IR. We conducted a genome-wide association study of the TG:HDL-C ratio in 402,398 Europeans within the UK Biobank. W...
Endocrine system and metabolic diseasesGenetics research
10.1038/S41588-023-01625-2
ISSN:1061-4036
Improving multi-trait genomic prediction by incorporating local genetic correlations
Jun Teng•Tingting Zhai•Xinyi Zhang•Changheng Zhao•Wenwen Wang等 10 人
Communications Biology
2025
•2025/2/25
•Vol.8 No.1 p.1-14
Genomic prediction holds significant potential for advancing precision medicine in humans, as well as accelerating genetic improvement in animals and plants. For multi-trait prediction, the conventional multi-trait models are primarily based on global genetic correlations between traits. With the de...
Genetic markersQuantitative trait
10.1038/S42003-025-07721-9
ISSN:2399-3642
Association of childhood-to-adulthood body size trajectories with cardiovascular risk and all cause mortality
Feifei Tang•Wenjuan Ye•Gongxia Xu•Houren Xiong•Yanyan Chen等 8 人
International Journal Of Obesity
2026
•2026/4/30
•00 p.1-7
The relationship between body size across the life course and risks of cardiovascular disease (CVD) and mortality remains incompletely understood, particularly regarding transitions from childhood to adulthood and potential sex-specific differences. We examined the independent and joint associations...
Cardiovascular diseasesRisk factors
10.1038/S41366-026-02091-6
ISSN:0307-0565
Brain asymmetries from mid- to late life and hemispheric brain age
Max Korbmacher•Dennis van der Meer•Dani Beck•Ann-Marie G. de Lange•Eli Eikefjord等 9 人
Nature Communications
2024
•2024/2/1
•Vol.15 No.1 p.1-14
The human brain demonstrates structural and functional asymmetries which have implications for ageing and mental and neurological disease development. We used a set of magnetic resonance imaging (MRI) metrics derived from structural and diffusion MRI data in N=48,040 UK Biobank participants to evalu...
BiomarkersBrainNeural ageing
10.1038/S41467-024-45282-3
ISSN:2041-1723
Atlas of Proteomic signatures of brain structure and its links to brain disorders
Peng Ren•Xiao-He Hou•Zeyu Li•Jia You•Yuzhu Li等 21 人
Nature Communications
2025
•2025/6/2
•Vol.16 No.1 p.1-18
Individual variation in brain structure influences deterioration due to disease and comprehensive profiling of the associated proteomic signature advances mechanistic understanding. Here, using data from 4997 UK Biobank participants, we analyzed the associations between 2920 plasma proteins and 272 ...
Magnetic resonance imagingNeurological disordersProteomicsPsychiatric disorders
10.1038/S41467-025-60185-7
ISSN:2041-1723
MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk
Ida Surakka•Lars G. Fritsche•Wei Zhou•Joshua Backman•Jack A. Kosmicki等 26 人
Nature Communications
2020
•2020/10/23
•Vol.11 No.1 p.1-8
A major challenge in genetic association studies is that most associated variants fall in the non-coding part of the human genome. We searched for variants associated with bone mineral density (BMD) after enriching the discovery cohort for loss-of-function (LoF) mutations by sequencing a subset of t...
Computational biology and bioinformaticsGenetic association studyGeneticsGenome-wide association studiesPredictive medicine
10.1038/S41467-020-17315-0
ISSN:2041-1723
Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection
Seyedeh M. Zekavat•Shu-Hong Lin•Alexander G. Bick•Aoxing Liu•Kaavya Paruchuri等 37 人
Nature Medicine
2021
•2021/6/7
•00 p.1-13
Age is the dominant risk factor for infectious diseases, but the mechanisms linking age to infectious disease risk are incompletely understood. Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA, are structural somatic variants indicative of clonal hemato...
Chromosome abnormalityInfectious diseases
10.1038/S41591-021-01371-0
ISSN:1078-8956
Multi-dimensional evidence from the UK Biobank shows the impact of diet and macronutrient intake on aging
Chen Zhu•Youfa Wang•Xiaosong Yang•Qiran Zhao•Wenyan Xu等 9 人
Communications Medicine
2025
•2025/2/4
•Vol.5 No.1 p.1-9
The role of diet in aging is crucial, yet research findings on how specific diets influence human aging remain inconsistent. Understanding the relationship between dietary factors and aging could inform interventions to promote healthier aging outcomes. We analyzed data from the UK Biobank baseline ...
Genetic interactionNutrigenomics
10.1038/S43856-025-00754-5
ISSN:2730-664X
Healthy dietary patterns for prevention of neuropsychiatric disorders: role of inflammatory and metabolic mechanisms
Yinghao Xu•Ziye Ren•Huimin Cai•Xiaofeng Fu•Shuiyue Quan等 11 人
Npj Science Of Food
2025
•2025/12/9
•Vol.9 No.1 p.2640
Diet is increasingly being recognized as a modifiable lifestyle factor that plays an important role in neuropsychiatric health. However, existing research has focused on single foods or dietary patterns in relation to specific diseases, limiting their ability to inform precise dietary recommendation...
DiseasesHealth careNeurologyNeuroscienceRisk factors
10.1038/S41538-025-00623-4
ISSN:2396-8370
Associations between carotid artery intima-media thickness, traditional risk factors and proteins
Lars Lind•Rui Zheng
Npj Cardiovascular Health
2025
•2025/7/2
•Vol.2 No.1 p.1-10
We aimed to assess the role of traditional cardiovascular risk factors on carotid artery intima-media thickness (IMT) and proteins associated with IMT. IMT was measured in 50,704 participants from the UK Biobank. Plasma levels of 2923 proteins were analyzed in 6328 individuals. Mendelian randomizati...
Cardiovascular biologyInterventional cardiology
10.1038/S44325-025-00073-7
ISSN:2948-2836
Large-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci
Xikun Han•Puya Gharahkhani•Andrew R. Hamel•Jue Sheng Ong•Miguel E. Rentería等 29 人
Nature Genetics
2023
•2023/6/29
•00 p.1-10
Glaucoma, a leading cause of irreversible blindness, is a highly heritable human disease. Previous genome-wide association studies have identified over 100 loci for the most common form, primary open-angle glaucoma. Two key glaucoma-associated traits also show high heritability: intraocular pressure...
Gene expressionGenome-wide association studies
10.1038/S41588-023-01428-5
ISSN:1061-4036
Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases
Jiyuan An•Puya Gharahkhani•Matthew H. Law•Jue-Sheng Ong•Xikun Han等 18 人
Nature Communications
2019
•2019/9/16
•Vol.10 No.1 p.1-10
Gastroesophageal reflux disease (GERD) is caused by gastric acid entering the esophagus. GERD has high prevalence and is the major risk factor for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EA). We conduct a large GERD GWAS meta-analysis (80,265 cases, 305,011 controls), identifying 25 ...
Cancer geneticsGastro-oesophageal reflux diseaseGenome-wide association studiesOesophageal cancer
10.1038/S41467-019-11968-2
ISSN:2041-1723
Diet modifies the association between alcohol consumption and severe alcohol-related liver disease incidence
Fanny Petermann-Rocha•Ziyi Zhou•John C. Mathers•Carlos Celis-Morales•David Raubenheimer等 9 人
Nature Communications
2024
•2024/8/11
•Vol.15 No.1 p.1-9
It is elusive why some heavy drinkers progress to severe alcohol-related liver disease (ALD) while others do not. This study aimed to investigate if the association between alcohol consumption and severe ALD is modified by diet. This prospective study included 303,269 UK Biobank participants. Alcoho...
Alcoholic liver diseaseEpidemiologyGastroenterologyRisk factors
10.1038/S41467-024-51314-9
ISSN:2041-1723
Associations of oral contraceptives and hormone replacement therapy with incident dementia risk: a population-based cohort study
Ya-Nan Ou•Xue Liu•Pei-Yang Gao•Liu Yang•Jian-Feng Feng等 8 人
Translational Psychiatry
2026
•2026/4/18
0The relationships between exogenous hormones and dementia, as well as cognitive function in females, remains debated. This study aimed to investigate the associations of exogenous hormone exposure (oral contraceptives [OC] and hormone replacement therapy [HRT]) with incident dementia risk, cognitive...
DiseasesNeuroscience
10.1038/S41398-026-04007-4
ISSN:2158-3188
Healthy dietary patterns and the risk of individual chronic diseases in community-dwelling adults
Xianwen Shang•Jiahao Liu•Zhuoting Zhu•Xueli Zhang•Yu Huang等 13 人
Nature Communications
2023
•2023/10/23
•Vol.14 No.1 p.1-14
It is unclear regarding associations of dietary patterns with a wide range of chronic diseases and which dietary score is more predictive of major chronic diseases. Using the UK Biobank, we examine associations of four individual healthy dietary scores with the risk of 48 individual chronic diseases...
Alzheimer's diseaseCancer epidemiologyPeripheral vascular diseaseRisk factorsType 2 diabetes
10.1038/S41467-023-42523-9
ISSN:2041-1723
Quantifying the causal impact of biological risk factors on healthcare costs
Jiwoo Lee•Sakari Jukarainen•Antti Karvanen•Padraig Dixon•Neil M. Davies等 8 人
Nature Communications
2023
•2023/9/13
•Vol.14 No.1 p.1-11
Understanding the causal impact that clinical risk factors have on healthcare-related costs is critical to evaluate healthcare interventions. Here, we used a genetically-informed design, Mendelian Randomization (MR), to infer the causal impact of 15 risk factors on annual total healthcare costs. We ...
EconomicsPredictive markersPublic healthRisk factors
10.1038/S41467-023-41394-4
ISSN:2041-1723
Large-scale proteomic analyses before depression diagnosis reveal novel pathophysiological insights
Bolun Cheng•Shiqiang Cheng•Chuyu Pan•Wenming Wei•Jin Feng等 9 人
Molecular Psychiatry
2026
•2026/3/21
•00 p.1-11
The early pathophysiology of depression is poorly understood. We elucidated the decadal temporal evolution of plasma proteomic alterations before depression diagnosis and evaluated their associations with comorbid conditions and neuroanatomical changes. This study analyzed 31,114 depression-free par...
DepressionPredictive markers
10.1038/S41380-026-03540-4
ISSN:1359-4184
The relationship between neuropsychiatric dimensions and markers of Parkinson’s disease risk in the UK Biobank
Bahaaeddin Attaallah•Sheena Waters•Charles Marshall•Alastair Noyce
Npj Parkinson's Disease
2025
•2025/12/1
•Vol.11 No.1 p.3440
Neuropsychiatric symptoms are a significant yet often overlooked aspect of Parkinson’s disease (PD). Using UK Biobank data, we examined associations between neuropsychiatric dimensions and PD risk markers. Factor analysis identified four dimensions—Depression, Anxiety, Adult Stress-Adversity, and Al...
BiomarkersDiseasesNeurologyNeuroscience
10.1038/S41531-025-01181-Y
ISSN:2373-8057
Accelerated brain ageing during the COVID-19 pandemic
Ali-Reza Mohammadi-Nejad•Martin Craig•Eleanor F. Cox•Xin Chen•R. Gisli Jenkins等 8 人
Nature Communications
2025
•2025/7/22
•Vol.16 No.1 p.1-13
The impact of SARS-CoV-2 and the COVID-19 pandemic on brain health is recognised, yet specific effects remain understudied. We investigate the pandemic’s impact on brain ageing using longitudinal neuroimaging data from the UK Biobank. Brain age prediction models are trained from hundreds of multi-mo...
Brain imagingViral infection
10.1038/S41467-025-61033-4
ISSN:2041-1723
Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
Byun Jinyoung•Han Younghun•Li Yafang•Xia Jun•Long Erping等 85 人
Nature Genetics
2022
•2022/8/1
•Vol.54 No.8 p.1167-1177
To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new le...
Genome-wide association studiesLung cancer
10.1038/S41588-022-01115-X
ISSN:1061-4036
Whole-genome sequencing of a sporadic primary immunodeficiency cohort
James E. D. Thaventhiran•Hana Lango Allen•Oliver S. Burren•William Rae•Daniel Greene等 50 人
Nature
2020
•2020/5/6
•Vol.583 No.7814 p.90-95
Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typicall...
GenomicsImmunology
10.1038/S41586-020-2265-1
ISSN:0028-0836
Effects of urban living environments on mental health in adults
Jiayuan Xu•Nana Liu•Elli Polemiti•Liliana Garcia-Mondragon•Jie Tang等 13 人
Nature Medicine
2023
•2023/6/15
•Vol.29 No.6 p.1456-1467
Urban-living individuals are exposed to many environmental factors that may combine and interact to influence mental health. While individual factors of an urban environment have been investigated in isolation, no attempt has been made to model how complex, real-life exposure to living in the city r...
Genome-wide association studiesRisk factors
10.1038/S41591-023-02365-W
ISSN:1078-8956
Polygenic risk for schizophrenia is associated with white matter microstructure, cognitive and mental health
Qian Qian•Guoshu Zhao•Nannan Zhang•Shaoying Wang•Jinghan Sun等 8 人
Schizophrenia
2025
•2025/12/30
•Vol.12 No.1 p.120
Schizophrenia is highly heritable, and polygenic risk score for schizophrenia (PRSSCZ) has been associated with brain and behavior in healthy populations. However, the full associations of PRSSCZ with brain white matter microstructure and cognitive and mental health outcomes, the potential effects o...
Human behaviourNeuroscienceSchizophrenia
10.1038/S41537-025-00714-X
ISSN:2754-6993
Gene–gene interaction detection with deep learning
Cui Tianyu•El Mekkaoui Khaoula•Reinvall Jaakko•Havulinna Aki S.•Marttinen Pekka等 6 人
Communications Biology
2022
•2022/11/12
•Vol.5 No.1 p.1-12
The extent to which genetic interactions affect observed phenotypes is generally unknown because current interaction detection approaches only consider simple interactions between top SNPs of genes. We introduce an open-source framework for increasing the power of interaction detection by considerin...
EpistasisGenome-wide association studiesMachine learningStatistical methods
10.1038/S42003-022-04186-Y
ISSN:2399-3642
Uncovering apparent incomplete penetrance of TSC1/TSC2 variants: Insights from multiple population cohorts and implications for newborn screening
J. Fasham•A. McPhater•R. Whittington•A. T. Pagnamenta•T. S. Hall等 10 人
European Journal Of Human Genetics
2026
•2026/5/18
•00 p.1-10
Tuberous sclerosis complex (TSC) is a genetic multisystem disorder regarded as having near-complete penetrance, a view largely derived from clinically ascertained cohorts. As genomic newborn screening is piloted internationally, robust estimates of penetrance and expressivity in unselected populatio...
Disease-free survivalDisease geneticsGenetics of the nervous systemMedical genomics
10.1038/S41431-026-02107-9
ISSN:1018-4813
Efficient and accurate framework for genome-wide gene-environment interaction analysis in large-scale biobanks
Yuzhuo Ma•Yanlong Zhao•Ji-Feng Zhang•Wenjian Bi
Nature Communications
2025
•2025/3/29
•Vol.16 No.1 p.1-21
Gene-environment interaction (G×E) analysis elucidates the interplay between genetic and environmental factors. Genome-wide association studies (GWAS) have expanded to encompass complex traits like time-to-event and ordinal traits, which provide richer phenotypic information. However, most existing ...
GeneticsGenome-wide association studies
10.1038/S41467-025-57887-3
ISSN:2041-1723
A probabilistic graphical model for estimating selection coefficients of nonsynonymous variants from human population sequence data
Yige Zhao•Tian Lan•Guojie Zhong•Jake Hagen•Hongbing Pan等 7 人
Nature Communications
2025
•2025/5/20
•Vol.16 No.1 p.1-12
Accurately predicting the effect of missense variants is important in discovering disease risk genes and clinical genetic diagnostics. Commonly used computational methods predict pathogenicity, which does not capture the quantitative impact on fitness in humans. We develop a method, MisFit, to estim...
Machine learningRare variantsSequence annotation
10.1038/S41467-025-59937-2
ISSN:2041-1723
Deep learning-based phenotype imputation on population-scale biobank data increases genetic discoveries
Ulzee An•Ali Pazokitoroudi•Marcus Alvarez•Lianyun Huang•Silviu Bacanu等 13 人
Nature Genetics
2023
•2023/11/20
•00 p.1-8
Biobanks that collect deep phenotypic and genomic data across many individuals have emerged as a key resource in human genetics. However, phenotypes in biobanks are often missing across many individuals, limiting their utility. We propose AutoComplete, a deep learning-based imputation method to impu...
Data miningGenome-wide association studiesSoftware
10.1038/S41588-023-01558-W
ISSN:1061-4036
Mapping rare protein-coding variants on multi-organ imaging traits
Yijun Fan•Jie Chen•Zirui Fan•Julio Chirinos•Jason L. Stein等 23 人
Nature Communications
2025
•2025/12/23
0Human organ structure and function are important endophenotypes for clinical outcomes. Genome-wide association studies (GWAS) have identified numerous common variants associated with phenotypes derived from magnetic resonance imaging (MRI) of the brain and body. However, the role of rare protein-cod...
Genetic association studyGenomics
10.1038/S41467-025-67431-Y
ISSN:2041-1723
Cross-organ analysis reveals associations between vascular properties of the retina, the carotid and aortic arteries, and the brain
Sofía Ortín Vela•Sven Bergmann
Communications Medicine
2026
•2026/2/9
•Vol.6 No.1 p.1020
Vascular properties of the retina are indicative of both ocular and systemic cardio- and cerebrovascular health. However, the specific relationships between retinal and non-retinal vascular phenotypes have not been systematically investigated in large samples. This study aims to compare cross-organ ...
Diagnostic markersGenetic databases
10.1038/S43856-025-01310-X
ISSN:2730-664X
Determinants of transthyretin levels and their association with adverse clinical outcomes among UK Biobank participants
Naman S. Shetty•Mokshad Gaonkar•Nirav Patel•Akhil Pampana•Nehal Vekariya等 8 人
Nature Communications
2024
•2024/7/23
•Vol.15 No.1 p.1-7
Transthyretin is a transport protein whose misfolding has been implicated in the development of cardiac amyloidosis. Here, we examine the clinical correlates of transthyretin levels, the differences in transthyretin levels according to the pathogenic V142I TTR variant carrier status, and the associa...
CardiologyPredictive markers
10.1038/S41467-024-50231-1
ISSN:2041-1723
Deep representation learning for clustering longitudinal survival data from electronic health records
Jiajun Qiu•Yao Hu•Li Li•Abdullah Mesut Erzurumluoglu•Ingrid Braenne等 16 人
Nature Communications
2025
•2025/3/14
•Vol.16 No.1 p.1-14
Precision medicine requires accurate identification of clinically relevant patient subgroups. Electronic health records provide major opportunities for leveraging machine learning approaches to uncover novel patient subgroups. However, many existing approaches fail to adequately capture complex inte...
EpidemiologyHealth servicesMachine learning
10.1038/S41467-025-56625-Z
ISSN:2041-1723
Unsupervised deep learning of electrocardiograms enables scalable human disease profiling
Sam F. Friedman•Shaan Khurshid•Rachael A. Venn•Xin Wang•Nate Diamant等 19 人
Npj Digital Medicine
2025
•2025/1/12
•Vol.8 No.1 p.1-13
The 12-lead electrocardiogram (ECG) is inexpensive and widely available. Whether conditions across the human disease landscape can be detected using the ECG is unclear. We developed a deep learning denoising autoencoder and systematically evaluated associations between ECG encodings and ~1,600 Pheco...
Predictive markersRisk factors
10.1038/S41746-024-01418-9
ISSN:2398-6352
Selenoprotein deficiency disorder predisposes to aortic aneurysm formation
Erik Schoenmakers•Federica Marelli•Helle F. Jørgensen•W. Edward Visser•Carla Moran等 31 人
Nature Communications
2023
•2023/12/2
•Vol.14 No.1 p.1-14
Aortic aneurysms, which may dissect or rupture acutely and be lethal, can be a part of multisystem disorders that have a heritable basis. We report four patients with deficiency of selenocysteine-containing proteins due to selenocysteine Insertion Sequence Binding Protein 2 (SECISBP2) mutations who ...
CardiologyMechanisms of diseaseValvular disease
10.1038/S41467-023-43851-6
ISSN:2041-1723
Hospital-treated infectious diseases and the risk of epilepsy in older age
Qiyuan Zhuang•Yihan Hu•Dang Wei•Chenxi Qin•Kejia Hu等 14 人
Nature Aging
2025
•2025/11/4
•00 p.1-9
Infectious diseases are known to trigger acute seizures, but their long-term impact on epilepsy, especially in later life, is unclear. We conducted nested case–control studies of newly diagnosed epilepsy after age 50 in the UK Biobank (2,486 cases; 12,430 controls) and Swedish registers (56,266 case...
AgeingEpilepsyInfectious diseases
10.1038/S43587-025-01005-X
ISSN:2662-8465
UK BioCoin: swift trait-specific summary statistics regression for UK Biobank
Jingcheng He•Guoan Qi•Jiacheng Ying•Yu Qian•Lin-Lin Gu等 11 人
Nature Communications
2026
•2026/4/17
0Summary statistics derived from large-scale biobanks facilitate the sharing of genetic discoveries but are typically limited by fixed covariate adjustments, preventing the exploration of trait-specific adjustments. Here we present UK BioCoin (UKC), a computational device designed to enable efficient...
Genome-wide association studiesStatistical methods
10.1038/S41467-026-71788-Z
ISSN:2041-1723
Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts
Elizabeth T. Cirulli•Simon White•Robert W. Read•Gai Elhanan•William J. Metcalf等 13 人
Nature Communications
2020
•2020/1/28
•Vol.11 No.1 p.1-10
Understanding the impact of rare variants is essential to understanding human health. We analyze rare (MAF < 0.1%) variants against 4264 phenotypes in 49,960 exome-sequenced individuals from the UK Biobank and 1934 phenotypes (1821 overlapping with UK Biobank) in 21,866 members of the Healthy Nevada...
Genetic association studyGenetics researchNext-generation sequencingRare variants
10.1038/S41467-020-14288-Y
ISSN:2041-1723
Statistical construction of calibrated prediction intervals for polygenic score-based phenotype prediction
Chang Xu•Santhi K. Ganesh•Xiang Zhou
Nature Genetics
2025
•2025/10/13
•00 p.1-10
Accurately quantifying uncertainty in predicted phenotypes from polygenic score (PGS)-based applications is essential for reliable clinical interpretation of PGS, supporting effective disease risk assessment and informed decision-making. Here, we present PredInterval, a nonparametric method for cons...
Genome-wide association studiesStatistics
10.1038/S41588-025-02360-6
ISSN:1061-4036
Associations of asthma with cardiometabolic diseases and multimorbidity: A cohort study in the UK Biobank
Junjie Lin•Yangyang Cheng•Yue Zhang•Mika Kivimäki•Rodrigo M. Carrillo-Larco等 7 人
Npj Primary Care Respiratory Medicine
2025
•2025/12/29
•Vol.36 No.1 p.100
Asthma is associated with adverse cardiovascular outcomes, but little is known about its role in the development of cardiometabolic multimorbidity (CMM). We aimed to examine the associations of asthma with both incident and coexisting cardiometabolic diseases (CMDs), characterizing their patterns an...
CardiologyDiseasesHealth careMedical researchRisk factors
10.1038/S41533-025-00474-2
ISSN:2055-1010
Machine learning-predicted insulin resistance is a risk factor for 12 types of cancer
Chia-Lin Lee•Tomohide Yamada•Wei-Ju Liu•Kazuo Hara•Toshimasa Yamauchi等 7 人
Nature Communications
2026
•2026/2/16
•Vol.17 No.1 p.13960
Insulin resistance is suggested to be a risk factor for cancer; however, large-scale epidemiological evidence linking insulin resistance to cancer remains limited. Here we apply a machine learning-based prediction model of insulin resistance with nine clinical parameters, termed artificial intellige...
Cancer epidemiologyCancer screeningEndocrine system and metabolic diseasesMachine learningRisk factors
10.1038/S41467-026-68355-X
ISSN:2041-1723
Computationally efficient whole-genome regression for quantitative and binary traits
Joelle Mbatchou•Leland Barnard•Joshua Backman•Anthony Marcketta•Jack A. Kosmicki等 17 人
Nature Genetics
2021
•2021/5/20
•00 p.1-7
Genome-wide association analysis of cohorts with thousands of phenotypes is computationally expensive, particularly when accounting for sample relatedness or population structure. Here we present a novel machine-learning method called REGENIE for fitting a whole-genome regression model for quantitat...
Genetic association studySoftware
10.1038/S41588-021-00870-7
ISSN:1061-4036
Genetic and phenotypic analysis of the causal relationship between aging and COVID-19
Ying Kejun•Zhai Ranran•Pyrkov Timothy V.•Shindyapina Anastasia V.•Mariotti Marco等 8 人
Communications Medicine
2021
•2021/10/5
•Vol.1 No.1 p.1-15
Epidemiological studies revealed that the elderly and those with comorbidities are most affected by COVID-19, but it is important to investigate shared genetic mechanisms between COVID-19 risk and aging. We conducted a multi-instrument Mendelian Randomization analysis of multiple lifespan-related tr...
AgeingDisease geneticsViral infection
10.1038/S43856-021-00033-Z
ISSN:2730-664X
Brain tissue- and cell type-specific eQTL Mendelian randomization reveals efficacy of FADS1 and FADS2 on cognitive function
Xueyan Wu•Lei Jiang•Hongyan Qi•Chunyan Hu•Xiaojing Jia等 19 人
Translational Psychiatry
2024
•2024/2/5
•Vol.14 No.1 p.1-9
Epidemiological studies suggested an association between omega-3 fatty acids and cognitive function. However, the causal role of the fatty acid desaturase (FADS) gene, which play a key role in regulating omega-3 fatty acids biosynthesis, on cognitive function is unclear. Hence, we used two-sample Me...
Drug discoveryMedical genetics
10.1038/S41398-024-02784-4
ISSN:2158-3188
Mendelian randomization study of the relationship between blood and urine biomarkers and schizophrenia in the UK Biobank cohort
Bolun Cheng•Yunfeng Bai•Li Liu•Peilin Meng•Shiqiang Cheng等 12 人
Communications Medicine
2024
•2024/3/7
•Vol.4 No.1 p.1-8
The identification of suitable biomarkers is of crucial clinical importance for the early diagnosis of treatment-resistant schizophrenia (TRS). This study aims to comprehensively analyze the association between TRS and blood and urine biomarkers. Candidate TRS-related single nucleotide polymorphisms...
Diagnostic markersSchizophrenia
10.1038/S43856-024-00467-1
ISSN:2730-664X
An African ancestry-specific nonsense variant in CD36 is associated with a higher risk of dilated cardiomyopathy
Jennifer E. Huffman•Liam Gaziano•Zeina R. Al Sayed•Renae L. Judy•Laura M. Raffield等 42 人
Nature Genetics
2025
•2025/10/31
•00 p.1-9
The high burden of dilated cardiomyopathy (DCM) in individuals of African descent remains incompletely explained. Here, to explore a genetic basis, we conducted a genome-wide association study in 1,802 DCM cases and 93,804 controls of African genetic ancestry (AFR). A nonsense variant ( rs3211938 :G...
CardiomyopathiesGenome-wide association studies
10.1038/S41588-025-02372-2
ISSN:1061-4036
Mitochondria-wide association study observed significant interactions of mitochondrial respiratory and the inflammatory in the development of anxiety and depression
Li Liu•Shiqiang Cheng•Xin Qi•Peilin Meng•Xuena Yang等 15 人
Translational Psychiatry
2023
•2023/6/21
•Vol.13 No.1 p.1-10
The aim of this study was to investigate the possible interaction of mitochondrial dysfunction and inflammatory cytokines in the risk of anxiety and depression. We utilized the UK Biobank for the sample of this study. A mitochondria-wide association(MiWAS) and interaction analysis was performed to i...
DepressionHuman behaviour
10.1038/S41398-023-02518-Y
ISSN:2158-3188
Healthy lifestyle, metabolomic signature, and risk of late-onset schizophrenia: evidence from the prospective cohort
Xinru Guo•Ge Yu•Songyu Wu•Tingyi Jia•Zhouyang Sun等 7 人
Schizophrenia
2026
•2026/4/14
0A healthy lifestyle is associated with a reduced risk of schizophrenia, but the underlying metabolic mechanisms remain unclear. The aim of this study was to identify a metabolomic signature of a healthy lifestyle, to assess its mediation between lifestyle and schizophrenia risk, and to evaluate its ...
BiomarkersSchizophrenia
10.1038/S41537-026-00752-Z
ISSN:2754-6993
Associations of timing of physical activity with all-cause and cause-specific mortality in a prospective cohort study
Feng Hongliang•Yang Lulu•Liang Yannis Yan•Ai Sizhi•Liu Yaping等 18 人
Nature Communications
2023
•2023/2/18
•Vol.14 No.1 p.1-10
There is a growing interest in the role of timing of daily behaviors in improving health. However, little is known about the optimal timing of physical activity to maximize health benefits. We perform a cohort study of 92,139 UK Biobank participants with valid accelerometer data and all-cause and ca...
Disease preventionMedical researchPublic health
10.1038/S41467-023-36546-5
ISSN:2041-1723
A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
Wightman Douglas P.•Jansen Iris E.•Savage Jeanne E.•Shadrin Alexey A.•Bahrami Shahram等 59 人
Nature Genetics
2021
•2021/9/7
•Vol.53 No.9 p.1276-1282
Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven pre...
Genome-wide association studiesNeuroscience
10.1038/S41588-021-00921-Z
ISSN:1061-4036
Study design features increase replicability in brain-wide association studies
Kaidi Kang•Jakob Seidlitz•Richard A. I. Bethlehem•Jiangmei Xiong•Megan T. Jones等 19 人
Nature
2024
•2024/11/27
•00 p.1-9
Brain-wide association studies (BWAS) are a fundamental tool in discovering brain–behaviour associations1,2. Several recent studies have shown that thousands of study participants are required for good replicability of BWAS1–3. Here we performed analyses and meta-analyses of a robust effect size ind...
NeurologyNeuroscience
10.1038/S41586-024-08260-9
ISSN:0028-0836
Shared genetic architectures of educational attainment in East Asian and European populations
Tzu-Ting Chen•Jaeyoung Kim•Max Lam•Yi-Fang Chuang•Yen-Ling Chiu等 25 人
Nature Human Behaviour
2024
•2024/1/5
•00 p.1-14
Educational attainment (EduYears), a heritable trait often used as a proxy for cognitive ability, is associated with various health and social outcomes. Previous genome-wide association studies (GWASs) on EduYears have been focused on samples of European (EUR) genetic ancestries. Here we present the...
EducationGenomics
10.1038/S41562-023-01781-9
ISSN:2397-3374
Multi-omic spatial effects on high-resolution AI-derived retinal thickness
V. E. Jackson•Y. Wu•R. Bonelli•J. P. Owen•L. W. Scott等 14 人
Nature Communications
2025
•2025/2/4
•Vol.16 No.1 p.1-19
Retinal thickness is a marker of retinal health and more broadly, is seen as a promising biomarker for many systemic diseases. Retinal thickness measurements are procured from optical coherence tomography (OCT) as part of routine clinical eyecare. We processed the UK Biobank OCT images using a convo...
Computational neuroscienceQuantitative trait lociRetinaRisk factors
10.1038/S41467-024-55635-7
ISSN:2041-1723
Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma
Yi Han•Qiong Jia•Pedram Shafiei Jahani•Benjamin P. Hurrell•Calvin Pan等 13 人
Nature Communications
2020
•2020/4/15
•Vol.11 No.1 p.1-13
Asthma is a chronic and genetically complex respiratory disease that affects over 300 million people worldwide. Here, we report a genome-wide analysis for asthma using data from the UK Biobank and the Trans-National Asthma Genetic Consortium. We identify 66 previously unknown asthma loci and demonst...
AsthmaGenome-wide association studiesImmunogenetics
10.1038/S41467-020-15649-3
ISSN:2041-1723
Whole genome sequence analysis of blood lipid levels in >66,000 individuals
Selvaraj Margaret Sunitha•Li Xihao•Li Zilin•Pampana Akhil•Zhang David Y.等 85 人
Nature Communications
2022
•2022/10/11
•Vol.13 No.1 p.1-18
Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diver...
Cardiovascular geneticsGenetic markersGenome-wide association studies
10.1038/S41467-022-33510-7
ISSN:2041-1723
Relationship between metabolic status, physical activity and cardiovascular disease in participants with obesity
Yingxin Liu•Ai Zhao•Guiju Sun•Ruoting Wang•Jingyi Zhang等 7 人
International Journal Of Obesity
2024
•2024/1/22
•00 p.1-8
We aimed to investigate the independent and joint associations between metabolic status, PA (physical activity) and risk of CVD (cardiovascular disease) in participants with obesity. We included 109,301 adults with obesity free of baseline CVD enrolled from 2006 to 2010 in the UK Biobank cohort (age...
Epidemiology
10.1038/S41366-024-01469-8
ISSN:0307-0565
Broad clinical manifestations of polygenic risk for coronary artery disease in the Women’s Health Initiative
Clarke Shoa L.•Parham Matthew•Lankester Joanna•Shadyab Aladdin H.•Liu Simin等 9 人
Communications Medicine
2022
•2022/8/25
•Vol.2 No.1 p.1-9
The genetic basis for coronary artery disease (CAD) risk is highly complex. Genome-wide polygenic risk scores (PRS) can help to quantify that risk, but the broader impacts of polygenic risk for CAD are not well characterized. We measured polygenic risk for CAD using the meta genomic risk score, a pr...
Cardiovascular geneticsMedical genomics
10.1038/S43856-022-00171-Y
ISSN:2730-664X
The proportion of Alzheimer’s disease attributable to apolipoprotein E
Dylan M. Williams•Sami Heikkinen•Mikko Hiltunen•Neil M. Davies•Emma L. Anderson
Npj Dementia
2026
•2026/1/9
•Vol.2 No.1 p.10
Variation in the APOE gene strongly affects Alzheimer’s disease (AD) risk. However, the proportion of AD burden attributable to this variation requires clarification, which would help to elucidate the scope of strategies targeting apolipoprotein E (APOE) for AD prevention and treatment. We estimated...
DiseasesGeneticsMedical researchNeurologyNeuroscienceRisk factors
10.1038/S44400-025-00045-9
ISSN:3005-1940
Transcription start sites experience a high influx of heritable variants fueled by early development
Miguel Cortés Guzmán•David Castellano•Clàudia Serrano Colomé•Vladimir Seplyarskiy•Donate Weghorn
Nature Communications
2025
•2025/11/26
•Vol.16 No.1 p.101200
Mutations drive evolution and genetic diversity, with the most consequential mutations occurring in coding exons and regulatory regions. However, the impact of transcription on germline mutagenesis remains poorly understood. Here, we identify a mutational hotspot at transcription start sites (TSSs) ...
Cancer geneticsMutationStatistical methodsTranscription
10.1038/S41467-025-66201-0
ISSN:2041-1723
Polygenic prediction of occupational status GWAS elucidates genetic and environmental interplay in intergenerational transmission, careers and health in UK Biobank
Evelina T. Akimova•Tobias Wolfram•Xuejie Ding•Felix C. Tropf•Melinda C. Mills
Nature Human Behaviour
2024
•2024/12/23
•00 p.1-15
Socioeconomic status (SES) impacts health and life-course outcomes. This genome-wide association study (GWAS) of sociologically informed occupational status measures (ISEI, SIOPS, CAMSIS) using the UK Biobank (N = 273,157) identified 106 independent single-nucleotide polymorphisms of which 8 are nov...
Behavioural geneticsSociology
10.1038/S41562-024-02076-3
ISSN:2397-3374
Greater value add from electronic health records than polygenic risk scores for predicting myocardial infarction in machine learning
Monica Isgut•Andrew Hornback•Han Bao•Yiting Sun•Katherine Choi等 9 人
Communications Medicine
2025
•2025/11/3
•Vol.5 No.1 p.1-14
Polygenic risk scores (PRSs) are increasingly being used to predict disease risk from genetic data. While promising in research, their clinical utility—especially when combined with non-genetic (NG) data such as lab results, physical measurements, and diagnostic history—remains uncertain. Myocardial...
CardiologyGenetics
10.1038/S43856-025-01138-5
ISSN:2730-664X
Human GLP1R variants affecting GLP1R cell surface expression are associated with impaired glucose control and increased adiposity
Wenwen Gao•Lei Liu•Eunna Huh•Florence Gbahou•Erika Cecon等 23 人
Nature Metabolism
2023
•2023/9/14
•00 p.1-12
The glucagon-like peptide 1 receptor (GLP1R) is a major drug target with several agonists being prescribed in individuals with type 2 diabetes and obesity1,2. The impact of genetic variability of GLP1R on receptor function and its association with metabolic traits are unclear with conflicting report...
Genetic association studyMetabolismNext-generation sequencingObesityRisk factors
10.1038/S42255-023-00889-6
ISSN:2522-5812
New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
Nick Shrine•Anna L. Guyatt•A. Mesut Erzurumluoglu•Victoria E. Jackson•Brian D. Hobbs等 109 人
Nature Genetics
2019
•2019/2/25
•Vol.51 No.3 p.481-493
Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly pre...
Genome-wide association studiesRespiratory tract diseases
10.1038/S41588-018-0321-7
ISSN:1061-4036
Dissecting cross-population polygenic heterogeneity across respiratory and cardiometabolic diseases
Yuji Yamamoto•Yuya Shirai•Kyuto Sonehara•Shinichi Namba•Takafumi Ojima等 21 人
Nature Communications
2025
•2025/4/28
•Vol.16 No.1 p.1-18
Biological mechanisms underlying multimorbidity remain elusive. To dissect the polygenic heterogeneity of multimorbidity in twelve complex traits across populations, we leveraged biobank resources of genome-wide association studies (GWAS) for 232,987 East Asian individuals (the 1st and 2nd cohorts o...
AsthmaChronic obstructive pulmonary diseaseDyslipidaemiasGenome-wide association studiesType 2 diabetes
10.1038/S41467-025-58149-Y
ISSN:2041-1723
Local and global patterns support medical imaging as a biomarker of ageing
Tamara T. Mueller•Sophie Starck•Rozafë Llalloshi•Georgios Kaissis•Alexander Ziller等 21 人
Communications Medicine
2026
•2026/6/13
•Vol.6 No.1 p.3350
Understanding human ageing across multiple organs is essential for characterising individual health trajectories and identifying abnormal ageing processes. Multi-organ imaging provides an opportunity to quantify biological ageing beyond chronological age. The aim of this study is to assess organ-spe...
Biomarkers
10.1038/S43856-026-01722-3
ISSN:2730-664X
Transcriptional and imaging-genetic association of cortical interneurons, brain function, and schizophrenia risk
Kevin M. Anderson•Meghan A. Collins•Rowena Chin•Tian Ge•Monica D. Rosenberg等 6 人
Nature Communications
2020
•2020/6/8
•Vol.11 No.1 p.1-15
Inhibitory interneurons orchestrate information flow across the cortex and are implicated in psychiatric illness. Although interneuron classes have unique functional properties and spatial distributions, the influence of interneuron subtypes on brain function, cortical specialization, and illness ri...
Cognitive neuroscienceGene expressionSchizophrenia
10.1038/S41467-020-16710-X
ISSN:2041-1723
EAT-Lancet and plant-based diets, plasma metabolomic signatures, and biological aging
Jie Li•Jiang Li•Xiaoqin Xu•Kun Zhang•Ningjian Wang等 8 人
Npj Aging
2025
•2025/12/12
0The EAT-Lancet diet has been recently recommended for its potential health and environmental benefits. Here, leveraging data from the UK Biobank, we performed a comparative analysis to examine the associations of adherence to the EAT-Lancet diet versus traditional plant-based diets with biological a...
BiomarkersDiseasesHealth careMedical research
10.1038/S41514-025-00306-0
ISSN:2731-6068
Sleep chart of biological ageing clocks in middle and late life
Cliodhna Kate O’Toole•Zhiyuan Song•Filippos Anagnostakis•Zhijian Yang•Ye Ella Tian等 26 人
Nature
2026
•2026/5/13
•00 p.1-11
Optimal sleep has a vital role in promoting healthy ageing and enhancing longevity. Here we propose Sleep Chart to assess the relationship between self-reported sleep duration and 23 biological ageing clocks derived from in vivo imaging1, plasma proteomics2 and metabolomics3. First, a systemic, U-sh...
Computational modelsSystems analysis
10.1038/S41586-026-10524-5
ISSN:0028-0836
The genetic architecture of biological age in nine human organ systems
Junhao Wen•Ye Ella Tian•Ioanna Skampardoni•Zhijian Yang•Yuhan Cui等 11 人
Nature Aging
2024
•2024/6/28
•00 p.1-18
Investigating the genetic underpinnings of human aging is essential for unraveling the etiology of and developing actionable therapies for chronic diseases. Here, we characterize the genetic architecture of the biological age gap (BAG; the difference between machine learning-predicted age and chrono...
AgeingData miningGenome-wide association studies
10.1038/S43587-024-00662-8
ISSN:2662-8465
Associations and interactions between premorbid cognitive health, apolipoprotein e4 genotype, and incident Alzheimer’s disease in UK Biobank (N = 252,340)
Mohammad A. Jareebi•Josie Fullerton•Angelina K. Kancheva•Rachana Tank•Lachlan Gilchrist等 15 人
Npj Dementia
2025
•2025/6/18
•Vol.1 No.1 p.1-7
It is unclear to what extent genetic risk offsets the protective effects of better premorbid cognitive health on the risk of Alzheimer’s disease (AD). We tested for associations between measures of premorbid cognitive health, apolipoprotein (APOE) e4 ‘risk’ genotype, and their interaction, with risk...
Genetic markersGeneticsPsychology
10.1038/S44400-025-00013-3
ISSN:3005-1940
Dissection of genetic variation and evidence for pleiotropy in male pattern baldness
Chloe X. Yap•Julia Sidorenko•Yang Wu•Kathryn E. Kemper•Jian Yang等 8 人
Nature Communications
2018
•2018/12/20
•Vol.9 No.1 p.1-12
Male pattern baldness (MPB) is a sex-limited, age-related, complex trait. We study MPB genetics in 205,327 European males from the UK Biobank. Here we show that MPB is strongly heritable and polygenic, with pedigree-heritability of 0.62 (SE = 0.03) estimated from close relatives, and SNP-heritabilit...
Genetic markersGenetic variationGenome-wide association studiesHeritable quantitative trait
10.1038/S41467-018-07862-Y
ISSN:2041-1723
Large mosaic copy number variations confer autism risk
Maxwell A. Sherman•Rachel E. Rodin•Giulio Genovese•Caroline Dias•Alison R. Barton等 10 人
Nature Neuroscience
2021
•2021/1/11
•Vol.24 No.2 p.197-203
Although germline de novo copy number variants (CNVs) are known causes of autism spectrum disorder (ASD), the contribution of mosaic (early-developmental) copy number variants (mCNVs) has not been explored. In this study, we assessed the contribution of mCNVs to ASD by ascertaining mCNVs in genotype...
Autism spectrum disordersGenetics of the nervous systemStatistical methodsStructural variation
10.1038/S41593-020-00766-5
ISSN:1097-6256
Partitioned polygenic risk scores identify distinct types of metabolic dysfunction-associated steatotic liver disease
Oveis Jamialahmadi•Antonio De Vincentis•Federica Tavaglione•Francesco Malvestiti•Ruifang Li-Gao等 16 人
Nature Medicine
2024
•2024/12/9
•00 p.1-10
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by an excess of lipids, mainly triglycerides, in the liver and components of the metabolic syndrome, which can lead to cirrhosis and liver cancer. While there is solid epidemiological evidence that MASLD clusters with ...
Genome-wide association studiesRisk factors
10.1038/S41591-024-03284-0
ISSN:1078-8956
A deep learning method for HLA imputation and trans-ethnic MHC fine-mapping of type 1 diabetes
Tatsuhiko Naito•Ken Suzuki•Jun Hirata•Yoichiro Kamatani•Koichi Matsuda等 7 人
Nature Communications
2021
•2021/3/12
•Vol.12 No.1 p.1-14
Conventional human leukocyte antigen (HLA) imputation methods drop their performance for infrequent alleles, which is one of the factors that reduce the reliability of trans-ethnic major histocompatibility complex (MHC) fine-mapping due to inter-ethnic heterogeneity in allele frequency spectra. We d...
Genome-wide association studiesMachine learningStatistical methods
10.1038/S41467-021-21975-X
ISSN:2041-1723
Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts
Sara R. Rashkin•Rebecca E. Graff•Linda Kachuri•Khanh K. Thai•Stacey E. Alexeeff等 19 人
Nature Communications
2020
•2020/9/4
•Vol.11 No.1 p.1-14
Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 canc...
Cancer epidemiologyCancer genetics
10.1038/S41467-020-18246-6
ISSN:2041-1723
A genetic map of human metabolism across the allele frequency spectrum
Martijn Zoodsma•Carl Beuchel•Summaira Yasmeen•Leonhard Kohleick•Aakash Nepal等 11 人
Nature Genetics
2025
•2025/10/3
•00 p.1-11
Genetic studies of human metabolism have been limited in scale and allelic breadth. Here we provide a data-driven map of the genetic regulation of circulating small molecules and lipoprotein characteristics (249 traits) measured using proton nuclear magnetic resonance spectroscopy across the allele ...
EpidemiologyGenome-wide association studies
10.1038/S41588-025-02355-3
ISSN:1061-4036
Rare predicted loss of function alleles in Bassoon (BSN) are associated with obesity
Na Zhu•Charles A. LeDuc•Ilene Fennoy•Blandine Laferrère•Claudia A. Doege等 8 人
Npj Genomic Medicine
2023
•2023/10/21
•Vol.8 No.1 p.1-6
Bassoon (BSN) is a component of a hetero-dimeric presynaptic cytomatrix protein that orchestrates neurotransmitter release with Piccolo (PCLO) from glutamatergic neurons throughout the brain. Heterozygous missense variants in BSN have previously been associated with neurodegenerative disorders in hu...
Medical genomicsMetabolic disorders
10.1038/S41525-023-00376-7
ISSN:2056-7944
The genetic architecture of human cerebellar morphology supports a key role for the cerebellum in human evolution and psychopathology
Torgeir Moberget•Dennis van der Meer•Shahram Bahrami•Daniel Roelfs•Oleksandr Frei等 15 人
Communications Biology
2026
•2026/2/17
•Vol.9 No.1 p.4450
The functional domain of the cerebellum has expanded beyond motor control to also include cognitive and affective functions. In line with this notion, cerebellar volume has increased over recent primate evolution, and cerebellar alterations have been linked to heritable mental disorders. To map the ...
BrainGenetics of the nervous systemPsychiatric disorders
10.1038/S42003-026-09664-1
ISSN:2399-3642
TP53-mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease
Zekavat Seyedeh M.•Viana-Huete Vanesa•Matesanz Nuria•Jorshery Saman Doroodgar•Zuriaga María A.等 31 人
Nature Cardiovascular Research
2023
•2023/1/16
•Vol.2 No.2 p.144-158
Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP) are associated with an increased risk of hematologic malignancy, coronary artery disease and all-cause mortality. Here we analyze the relation between CHIP status and incident peripheral artery disease (P...
Cardiovascular geneticsComputational biology and bioinformaticsGenetics
10.1038/S44161-022-00206-6
ISSN:2731-0590
High diversity of dietary flavonoid intake is associated with a lower risk of all-cause mortality and major chronic diseases
Benjamin H. Parmenter•Alysha S. Thompson•Nicola P. Bondonno•Amy Jennings•Kevin Murray等 10 人
Nature Food
2025
•2025/6/2
•00 p.1-13
Higher habitual intakes of dietary flavonoids have been linked with a lower risk of all-cause mortality and major chronic disease. Yet, the contribution of diversity of flavonoid intake to health outcomes remains to be investigated. Here, using a cohort of 124,805 UK Biobank participants, we show th...
DiseasesEpidemiologyNutrition
10.1038/S43016-025-01176-1
ISSN:2662-1355
Epistasis regulates genetic control of cardiac hypertrophy
Qianru Wang•Tiffany M. Tang•Michelle Youlton•Chad S. Weldy•Ana M. Kenney等 24 人
Nature Cardiovascular Research
2025
•2025/6/5
•00 p.1-21
Although genetic variant effects often interact nonadditively, strategies to uncover epistasis remain in their infancy. Here we develop low-signal signed iterative random forests to elucidate the complex genetic architecture of cardiac hypertrophy, using deep learning-derived left ventricular mass e...
Cardiac hypertrophyCardiovascular geneticsLab-on-a-chipMachine learningStem-cell biotechnology
10.1038/S44161-025-00656-8
ISSN:2731-0590
Associations of long-term exposure to nitrogen oxides with all-cause and cause-specific mortality
Siru Yang•Mengmeng Li•Cui Guo•Weeberb J. Requia•Mohammad Javad Zare Sakhvidi等 12 人
Nature Communications
2025
•2025/2/18
•Vol.16 No.1 p.1-12
Associations between long-term exposure to nitrogen oxides (NOx) and cause-specific mortality remain insufficiently explored. This study utilizes data from 502,040 participants registered in the UK Biobank. Time-varying Cox regression is used to estimate mortality risks associated with NOx. Cause-sp...
DiseasesRisk factors
10.1038/S41467-025-56963-Y
ISSN:2041-1723
Multi-ancestry genome-wide association analyses of refractive error augment genetic discovery and polygenic prediction
Fei-Fei Cheng•Xiaoxi Liu•Hao Mi•Lizhong Wang•Ruilei Ma等 27 人
Nature Genetics
2026
•2026/4/20
•00 p.1-10
Refractive errors (REs) affect over half of the global population, with consequences ranging from blurred vision to blindness. Here we conducted ancestry-stratified and cross-ancestry meta-analyses of genome-wide association studies for RE in people of European (n = 1,495,159), East Asian (n = 121,1...
DiseasesGenome-wide association studies
10.1038/S41588-026-02576-0
ISSN:1061-4036
A polygenic score method boosted by non-additive models
Rikifumi Ohta•Yosuke Tanigawa•Yuta Suzuki•Manolis Kellis•Shinichi Morishita
Nature Communications
2024
•2024/5/29
•Vol.15 No.1 p.1-13
Dominance heritability in complex traits has received increasing recognition. However, most polygenic score (PGS) approaches do not incorporate non-additive effects. Here, we present GenoBoost, a flexible PGS modeling framework capable of considering both additive and non-additive effects, specifica...
Genetic association studyGenetics research
10.1038/S41467-024-48654-X
ISSN:2041-1723
Association between accelerometer-measured irregular sleep duration and longitudinal changes in body mass index in older adults
Sina Kianersi•Kaitlin S. Potts•Heming Wang•Tamar Sofer•Raymond Noordam等 8 人
International Journal Of Obesity
2025
•2025/4/6
•00 p.1-10
Irregular sleep duration may disrupt circadian rhythms and contribute to metabolic, behavioral, and mood changes, potentially increasing the risk for obesity. However, quantitative data on the relationship between sleep duration irregularity and weight change are lacking. In this prospective study, ...
EpidemiologyLifestyle modification
10.1038/S41366-025-01768-8
ISSN:0307-0565
Multi-organ network of cardiometabolic disease-depression multimorbidity revealed by phenotypic and genetic analyses of MR images
Jingxuan Wang•Mianxin Liu•Feng Liu•Guangrui Yang•Zhongshang Yuan等 19 人
Nature Communications
2026
•2026/1/7
•Vol.17 No.1 p.13330
The development and progression of cardiometabolic diseases and depression multimorbidity involves pathophysiological processes across multiple organs. Using multi-organ imaging data from 31,246 UK Biobank participants, we investigate the multi-organ manifestations and their phenotypic connections a...
Cardiovascular diseasesDepressionGenomicsPredictive markers
10.1038/S41467-025-68092-7
ISSN:2041-1723
Large-scale proteomic analyses of incident Alzheimer’s disease reveal new pathophysiological insights and potential therapeutic targets
Yi Zhang•Yu Guo•Yu He•Jia You•YaRu Zhang等 16 人
Molecular Psychiatry
2024
•2024/11/19
•00 p.1-15
Pathophysiological evolutions in early-stage Alzheimer’s disease (AD) are not well understood. We used data of 2923 Olink plasma proteins from 51,296 non-demented middle-aged adults. During a follow-up of 15 years, 689 incident AD cases occurred. Cox-proportional hazard models were applied to identi...
BiomarkersDiseasesNeuroscience
10.1038/S41380-024-02840-X
ISSN:1359-4184
Sleep, physical activity, sedentary behavior, and risk of incident dementia: a prospective cohort study of 431,924 UK Biobank participants
Huang Shu-Yi•Li Yu-Zhu•Zhang Ya-Ru•Huang Yu-Yuan•Wu Bang-Sheng等 18 人
Molecular Psychiatry
2022
•2022/6/14
•00 p.1-12
Although sleep, physical activity and sedentary behavior have been found to be associated with dementia risk, findings are inconsistent and their joint relationship remains unclear. This study aimed to investigate independent and joint associations of these three modifiable behaviors with dementia r...
DiseasesNeuroscience
10.1038/S41380-022-01655-Y
ISSN:1359-4184
Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma
Berta Davide G.•Kuisma Heli•Välimäki Niko•Räisänen Maritta•Jäntti Maija等 27 人
Nature
2021
•2021/8/4
•00 p.1-6
One in four women suffers from uterine leiomyomas (ULs)—benign tumours of the uterine wall, also known as uterine fibroids—at some point in premenopausal life. ULs can cause excessive bleeding, pain and infertility1, and are a common cause of hysterectomy2. They emerge through at least three distinc...
Cancer epigeneticsCancer genomicsDisease geneticsInfertility
10.1038/S41586-021-03747-1
ISSN:0028-0836
The genetic relationships between brain structure and schizophrenia
Eva-Maria Stauffer•Richard A. I. Bethlehem•Lena Dorfschmidt•Hyejung Won•Varun Warrier等 6 人
Nature Communications
2023
•2023/11/28
•Vol.14 No.1 p.1-15
Genetic risks for schizophrenia are theoretically mediated by genetic effects on brain structure but it has been unclear which genes are associated with both schizophrenia and cortical phenotypes. We accessed genome-wide association studies (GWAS) of schizophrenia (N = 69,369 cases; 236,642 controls...
Development of the nervous systemGenetics of the nervous systemSchizophrenia
10.1038/S41467-023-43567-7
ISSN:2041-1723
Incident allergic diseases in post-COVID-19 condition: multinational cohort studies from South Korea, Japan and the UK
Jiyeon Oh•Myeongcheol Lee•Minji Kim•Hyeon Jin Kim•Seung Won Lee等 12 人
Nature Communications
2024
•2024/4/2
•Vol.15 No.1 p.1-10
As mounting evidence suggests a higher incidence of adverse consequences, such as disruption of the immune system, among patients with a history of COVID-19, we aimed to investigate post-COVID-19 conditions on a comprehensive set of allergic diseases including asthma, allergic rhinitis, atopic derma...
EpidemiologySARS-CoV-2Viral infection
10.1038/S41467-024-47176-W
ISSN:2041-1723
Latent profiles of modifiable dementia risk factors in later midlife: relationships with incident dementia, cognition, and neuroimaging outcomes
Lisa Y. Xiong•Madeline Wood Alexander•Yuen Yan Wong•Che-Yuan Wu•Myuri Ruthirakuhan等 11 人
Molecular Psychiatry
2024
•2024/8/5
•00 p.1-11
In 2020, the Lancet Commission identified 12 modifiable factors that increase population-level dementia risk. It is unclear if these risk factors co-occur among individuals in a clinically meaningful way. Using latent class analysis, we identified profiles of modifiable dementia risk factors in deme...
DiseasesNeuroscience
10.1038/S41380-024-02685-4
ISSN:1359-4184
Environmental and genetic predictors of human cardiovascular ageing
Mit Shah•Marco H. de A. Inácio•Chang Lu•Pierre-Raphaël Schiratti•Sean L. Zheng等 18 人
Nature Communications
2023
•2023/8/21
•Vol.14 No.1 p.1-15
Cardiovascular ageing is a process that begins early in life and leads to a progressive change in structure and decline in function due to accumulated damage across diverse cell types, tissues and organs contributing to multi-morbidity. Damaging biophysical, metabolic and immunological factors excee...
Cardiovascular diseasesCardiovascular geneticsGenome-wide association studies
10.1038/S41467-023-40566-6
ISSN:2041-1723
The genetic landscape of basal ganglia and implications for common brain disorders
Shahram Bahrami•Kaja Nordengen•Jaroslav Rokicki•Alexey A. Shadrin•Zillur Rahman等 17 人
Nature Communications
2024
•2024/10/1
•Vol.15 No.1 p.1-14
The basal ganglia are subcortical brain structures involved in motor control, cognition, and emotion regulation. We conducted univariate and multivariate genome-wide association analyses (GWAS) to explore the genetic architecture of basal ganglia volumes using brain scans obtained from 34,794 Europe...
Genetics of the nervous systemGenetics researchGenome-wide association studies
10.1038/S41467-024-52583-0
ISSN:2041-1723
A plasma protein-based risk score to predict hip fractures
Thomas R. Austin•Maria Nethander•Howard A. Fink•Anna E. Törnqvist•Diana I. Jalal等 29 人
Nature Aging
2024
•2024/5/27
•00 p.1-12
As there are effective treatments to reduce hip fractures, identification of patients at high risk of hip fracture is important to inform efficient intervention strategies. To obtain a new tool for hip fracture prediction, we developed a protein-based risk score in the Cardiovascular Health Study us...
Predictive markers
10.1038/S43587-024-00639-7
ISSN:2662-8465
Humans with function-disrupting variants in the myostatin gene (MSTN) have increased skeletal muscle mass and strength, and less adiposity
Joseph L. Herman•Peter Dornbos•Karl Landheer•Benjamin J. Geraghty•Marc A. Egerman等 20 人
Nature Communications
2026
•2026/3/13
0Myostatin negatively regulates skeletal muscle size in multiple species, and therefore, myostatin blockade has been therapeutically explored to promote muscle growth in humans, including to counter the muscle loss seen in obese humans using GLP1R agonists. In this study, we present results from a la...
Heritable quantitative traitMedical genetics
10.1038/S41467-026-70422-2
ISSN:2041-1723
Dairying, diseases and the evolution of lactase persistence in Europe
Evershed Richard P.•Davey Smith George•Roffet-Salque Mélanie•Timpson Adrian•Diekmann Yoan等 108 人
Nature
2022
•2022/7/27
•Vol.608 No.7922 p.336-345
In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years1. Although the selection of LP and the consumption of prehistoric milk must be linked, considerable...
ArchaeologyEvolutionary biology
10.1038/S41586-022-05010-7
ISSN:0028-0836
A sequence of SVA retrotransposon insertions in ASIP shaped human pigmentation
Nolan Kamitaki•Margaux L. A. Hujoel•Ronen E. Mukamel•Edward Gebara•Steven A. McCarroll等 6 人
Nature Genetics
2024
•2024/7/24
•Vol.56 No.8 p.1583-1591
Retrotransposons comprise about 45% of the human genome1, but their contributions to human trait variation and evolution are only beginning to be explored2,3. Here, we find that a sequence of SVA retrotransposon insertions in an early intron of the ASIP (agouti signaling protein) gene has probably s...
Gene expressionGenetic association studyPopulation geneticsSkin cancer
10.1038/S41588-024-01841-4
ISSN:1061-4036
Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain
Fan Chun Chieh•Loughnan Robert•Makowski Carolina•Pecheva Diliana•Chen Chi-Hua等 12 人
Nature Communications
2022
•2022/5/3
•Vol.13 No.1 p.1-10
The molecular determinants of tissue composition of the human brain remain largely unknown. Recent genome-wide association studies (GWAS) on this topic have had limited success due to methodological constraints. Here, we apply advanced whole-brain analyses on multi-shell diffusion imaging data and m...
BrainGenetics of the nervous systemGenome-wide association studies
10.1038/S41467-022-30110-3
ISSN:2041-1723
S100A8/A9 as a prognostic biomarker with causal effects for post-acute myocardial infarction heart failure
Jie Ma•Yang Li•Ping Li•Xinying Yang•Shuolin Zhu等 12 人
Nature Communications
2024
•2024/3/27
•Vol.15 No.1 p.1-13
Heart failure is the prevalent complication of acute myocardial infarction. We aim to identify a biomarker for heart failure post-acute myocardial infarction. This observational study includes 1062 and 1043 patients with acute myocardial infarction in the discovery and validation cohorts, respective...
BiomarkersMyocardial infarctionPredictive markers
10.1038/S41467-024-46973-7
ISSN:2041-1723
From wrist data to lifespan: elucidating inflammation-driven biological aging via activity rhythms captured by wearable devices
Jinjoo Shim•Faraz Bishehsari•Mahboobeh Mahdavinia•Jamie M. Zeitzer•Elgar Fleisch等 6 人
Npj Aging
2026
•2026/2/26
•Vol.12 No.1 p.490
Systemic inflammation (“inflammaging”) accelerates biological aging and drives cardiovascular, metabolic, and neurodegenerative disease. Circadian rhythms regulate the amplitude and timing of immune responses, yet their mechanistic role in inflammation and longevity remains unexplored. In 62,000 adu...
BiomarkersDiseasesNeurosciencePhysiology
10.1038/S41514-026-00349-X
ISSN:2731-6068
The association between childhood body size, adulthood lifestyle, and risk of 50 health conditions
Xiaomin Zeng•Ruiye Chen•Daiyue Yu•Danli Shi•Yujie Wang等 11 人
Communications Medicine
2026
•2026/1/12
•Vol.6 No.1 p.580
The long-term health consequences of childhood body size and whether it can be mitigated by a healthy adult lifestyle remains unclear. This study aims to explore the associations between childhood body size and the risk of mortality and major non-communicable diseases (NCDs), and the role of a lifes...
Lifestyle modificationPaediatric research
10.1038/S43856-025-01129-6
ISSN:2730-664X
White matter microstructure differences between 15q11.2 copy number variation carriers and non-carriers in mid-to-late life
Max Korbmacher•Rune Boen•Ole A. Andreassen•Lars T. Westlye•Ida E. Sønderby等 6 人
Translational Psychiatry
2026
•2026/3/19
•Vol.16 No.1 p.1900
The 15q11.2 BP1-BP2 copy number variant (CNV) has been associated with neurodevelopmental and psychiatric conditions and brain grey matter structure, but its effects on white matter microstructure (WMM) in mid-to-late adulthood to assess long-term neurobiological effects remain unclear. Understandin...
GeneticsNeuroscience
10.1038/S41398-026-03962-2
ISSN:2158-3188
Exposome-wide patterns predict brain health in aging
Mostafa Mahdipour•Somayeh Maleki Balajoo•Federico Raimondo•Jianxiao Wu•Eliana Nicolaisen-Sobesky等 11 人
Nature Communications
2026
•2026/4/10
•Vol.17 No.1 p.34090
Promoting brain health is vital for well-being and reducing healthcare burdens. Brain health as measured with the Brain Age Gap (BAG) - the difference between chronological and predicted brain age- relates to many factors. However, a holistic view, integrating the range of factors an individual brai...
NeuroscienceRisk factors
10.1038/S41467-026-71271-9
ISSN:2041-1723
Biological aging and generational shifts in early-onset cancer risk
Ruiyi Tian•Xiaoyu Zong•Duo Ren•Stefani Tica•Daniel Hong等 9 人
Nature Medicine
2026
•2026/6/22
•00 p.1-8
Incidence of early-onset cancer is rising globally in recent generations, which underscores the need to elucidate the influence of emerging generational risk factors. Systemic and organ-specific aging reflects the cumulative impact of exposures and may provide an integrative and complementary approa...
Cancer epidemiologyRisk factors
10.1038/S41591-026-04448-W
ISSN:1078-8956
Elevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity
Yimin Zhao•Zhenhuang Zhuang•Yueying Li•Wendi Xiao•Zimin Song等 11 人
Nature Communications
2024
•2024/3/19
•Vol.15 No.1 p.1-9
The connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remna...
BiomarkersCardiovascular diseasesEpidemiology
10.1038/S41467-024-46686-X
ISSN:2041-1723
Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks
Andrew S. Perry•Eric Farber-Eger•Tomas Gonzales•Toshiko Tanaka•Jeremy M. Robbins等 38 人
Nature Medicine
2024
•2024/6/4
•00 p.1-11
Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 indiv...
EpidemiologyPrognostic markers
10.1038/S41591-024-03039-X
ISSN:1078-8956
Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis
Kar Siddhartha P.•Quiros Pedro M.•Gu Muxin•Jiang Tao•Mitchell Jonathan等 14 人
Nature Genetics
2022
•2022/7/14
•Vol.54 No.8 p.1155-1166
Clonal hematopoiesis (CH), the clonal expansion of a blood stem cell and its progeny driven by somatic driver mutations, affects over a third of people, yet remains poorly understood. Here we analyze genetic data from 200,453 UK Biobank participants to map the landscape of inherited predisposition t...
Genetics researchGenome-wide association studiesHaematological diseases
10.1038/S41588-022-01121-Z
ISSN:1061-4036
Reply to: Milk intake, lactase non-persistence and type 2 diabetes risk in Chinese adults
Kai Luo•Yanbo Zhang•Robert C. Kaplan•Qibin Qi
Nature Metabolism
2024
•2024/9/18
•00 p.1-3
Endocrine system and metabolic diseasesEpidemiologyMetabolismRisk factors
10.1038/S42255-024-01129-1
ISSN:2522-5812
A method for an unbiased estimate of cross-ancestry genetic correlation using individual-level data
Momin Md. Moksedul•Shin Jisu•Lee Soohyun•Truong Buu•Benyamin Beben等 6 人
Nature Communications
2023
•2023/2/9
•Vol.14 No.1 p.1-13
Cross-ancestry genetic correlation is an important parameter to understand the genetic relationship between two ancestry groups. However, existing methods cannot properly account for ancestry-specific genetic architecture, which is diverse across ancestries, producing biased estimates of cross-ances...
Genome-wide association studiesHeritable quantitative traitObesity
10.1038/S41467-023-36281-X
ISSN:2041-1723
Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease
Jennifer S. Lees•Claire E. Welsh•Carlos A. Celis-Morales•Daniel Mackay•James Lewsey等 14 人
Nature Medicine
2019
•2019/11/7
•Vol.25 No.11 p.1753-1760
Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most cli...
BiomarkersPredictive markers
10.1038/S41591-019-0627-8
ISSN:1078-8956
Large-scale identification of protein biomarkers and therapeutic targets in heart and brain disease
Chao Wu•Dantong Li•Sumeet A. Khetarpal•Zixun Yuan•Shengyuan Huang等 13 人
Nature Cardiovascular Research
2026
•2026/4/2
•00 p.1-15
Neurological complications frequently impact morbidity, mortality and quality of life in patients with cardiovascular disease, yet the biological mediators connecting cardiovascular and neurological disease are poorly understood. Here we leverage data from 53,014 individuals with plasma proteomic pr...
BiomarkersCardiovascular biologyDiseases of the nervous systemTranslational research
10.1038/S44161-026-00799-2
ISSN:2731-0590
Exome sequencing identifies genes associated with sleep-related traits
Chen-Jie Fei•Ze-Yu Li•Jing Ning•Liu Yang•Bang-Sheng Wu等 15 人
Nature Human Behaviour
2024
•2024/1/4
•00 p.1-14
Sleep is vital for human health and has a moderate heritability. Previous genome-wide association studies have limitations in capturing the role of rare genetic variants in sleep-related traits. Here we conducted a large-scale exome-wide association study of eight sleep-related traits (sleep duratio...
Behavioural geneticsGenetic association studyGenetics researchSleep disorders
10.1038/S41562-023-01785-5
ISSN:2397-3374
Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
Zhishan Chen•Xingyi Guo•Ran Tao•Jeroen R. Huyghe•Philip J. Law等 205 人
Nature Communications
2024
•2024/4/26
•Vol.15 No.1 p.1-17
Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 1...
Cancer epidemiologyEpidemiology
10.1038/S41467-024-47399-X
ISSN:2041-1723
Machine learning reveals heterogeneous associations between environmental factors and cardiometabolic diseases across polygenic risk scores
Tatsuhiko Naito•Kosuke Inoue•Shinichi Namba•Kyuto Sonehara•Ken Suzuki等 11 人
Communications Medicine
2024
•2024/9/20
•Vol.4 No.1 p.1-12
Although polygenic risk scores (PRSs) are expected to be helpful in precision medicine, it remains unclear whether high-PRS groups are more likely to benefit from preventive interventions for diseases. Recent methodological advancements enable us to predict treatment effects at the individual level....
GeneticsPreventive medicine
10.1038/S43856-024-00596-7
ISSN:2730-664X
Body weight in neurological and psychiatric disorders: a large prospective cohort study
Rong-Ze Wang•Yu He•Yue-Ting Deng•Hui-Fu Wang•Yi Zhang等 8 人
Nature Mental Health
2024
•2024/1/4
•00 p.1-11
There is increasing attention on the associations between body weight and several neurological and psychiatric disorders. Using a total of 438,483 participants from the UK Biobank, we aimed to understand the effects of body mass index (BMI), BMI change and BMI-metabolic health status on the incidenc...
Neurological disordersPsychiatric disorders
10.1038/S44220-023-00158-1
ISSN:2731-6076
Sex differences in the association of wearable accelerometer-derived physical activity with coronary heart disease incidence and mortality
Jiajin Chen•Yuliang Wang•Zihang Zhong•Xin Chen•Le Zhang等 8 人
Nature Cardiovascular Research
2025
•2025/10/27
•00 p.1-11
Despite American Heart Association, European Society of Cardiology and World Health Organization (AHA/ESC/WHO) guidelines uniformly recommending 150 min week−1 of moderate-to-vigorous physical activity (MVPA) for both sexes, a substantial ‘gender gap’ persists in exercise capacity and guideline adhe...
Cardiovascular diseasesDisease prevention
10.1038/S44161-025-00732-Z
ISSN:2731-0590
The causes and consequences of Alzheimer’s disease: phenome-wide evidence from Mendelian randomization
Korologou-Linden Roxanna•Bhatta Laxmi•Brumpton Ben M.•Howe Laura D.•Millard Louise A. C.等 12 人
Nature Communications
2022
•2022/8/11
•Vol.13 No.1 p.1-14
Alzheimer’s disease (AD) has no proven causal and modifiable risk factors, or effective interventions. We report a phenome-wide association study (PheWAS) of genetic liability for AD in 334,968 participants of the UK Biobank study, stratified by age. We also examined the effects of AD genetic liabil...
Cognitive ageingDiseases of the nervous systemGenetic variation
10.1038/S41467-022-32183-6
ISSN:2041-1723
Conditional and interaction gene-set analysis reveals novel functional pathways for blood pressure
Christiaan A. de Leeuw•Sven Stringer•Ilona A. Dekkers•Tom Heskes•Danielle Posthuma
Nature Communications
2018
•2018/9/14
•Vol.9 No.1 p.1-13
Gene-set analysis provides insight into which functional and biological properties of genes are aetiologically relevant for a particular phenotype. But genes have multiple properties, and these properties are often correlated across genes. This can cause confounding in a gene-set analysis, because o...
Cardiovascular geneticsComputational biology and bioinformaticsGenetic association study
10.1038/S41467-018-06022-6
ISSN:2041-1723
Rare coding variant analysis for human diseases across biobanks and ancestries
Sean J. Jurgens•Xin Wang•Seung Hoan Choi•Lu-Chen Weng•Satoshi Koyama等 25 人
Nature Genetics
2024
•2024/8/29
•00 p.1-10
Large-scale sequencing has enabled unparalleled opportunities to investigate the role of rare coding variation in human phenotypic variability. Here, we present a pan-ancestry analysis of sequencing data from three large biobanks, including the All of Us research program. Using mixed-effects models,...
DiseasesDNA sequencingGenetic association study
10.1038/S41588-024-01894-5
ISSN:1061-4036
Utility of biological aging acceleration in capturing transitions of atrial fibrillation and dementia: a population-based study
Yufan Liu•Chenglong Li
Npj Aging
2025
•2025/10/9
•Vol.11 No.1 p.1-10
The biological aging acceleration predicts both morbidity and mortality, while few investigations have examined its utility in evaluating transitions, e.g. development patterns, of atrial fibrillation (AF) and dementia. We aimed to investigate the utility of biological aging acceleration in predicti...
BiomarkersDiseases
10.1038/S41514-025-00274-5
ISSN:2731-6068
A worldwide study of white matter microstructural alterations in people living with Parkinson’s disease
Conor Owens-Walton•Talia M. Nir•Sarah Al-Bachari•Sonia Ambrogi•Tim J. Anderson等 58 人
Npj Parkinson's Disease
2024
•2024/8/11
•Vol.10 No.1 p.1-12
The progression of Parkinson’s disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MR...
Parkinson's disease
10.1038/S41531-024-00758-3
ISSN:2373-8057
Associations between mental health, blood pressure and the development of hypertension
Schaare H. Lina•Blöchl Maria•Kumral Deniz•Uhlig Marie•Lemcke Lorenz等 7 人
Nature Communications
2023
•2023/4/7
•Vol.14 No.1 p.1-17
Multiple studies have reported a link between mental health and high blood pressure with mixed or even contradictory findings. Here, we resolve those contradictions and further dissect the cross-sectional and longitudinal relationship between mental health, systolic blood pressure, and hypertension ...
DepressionHypertensionQuality of life
10.1038/S41467-023-37579-6
ISSN:2041-1723
Variance-quantitative trait loci enable systematic discovery of gene-environment interactions for cardiometabolic serum biomarkers
Westerman Kenneth E.•Majarian Timothy D.•Giulianini Franco•Jang Dong-Keun•Miao Jenkai等 11 人
Nature Communications
2022
•2022/7/9
•Vol.13 No.1 p.1-11
Gene-environment interactions represent the modification of genetic effects by environmental exposures and are critical for understanding disease and informing personalized medicine. These often induce differential phenotypic variance across genotypes; these variance-quantitative trait loci can be p...
Genetic interactionGenome-wide association studiesPredictive markersQuantitative trait loci
10.1038/S41467-022-31625-5
ISSN:2041-1723
Artificial intelligence-derived photoplethysmography age as a digital biomarker for cardiovascular health
Guangkun Nie•Qinghao Zhao•Gongzheng Tang•Yaxin Li•Shenda Hong
Communications Medicine
2025
•2025/11/19
•Vol.5 No.1 p.4810
Photoplethysmography (PPG), increasingly available through wearable devices, provides a non-invasive means of monitoring human hemodynamics. In this study, we introduce artificial intelligence-derived photoplethysmography (AI-PPG) age, a deep learning-based estimate of biological age from raw PPG si...
Population screeningPredictive markers
10.1038/S43856-025-01188-9
ISSN:2730-664X
GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification
Vasiliki Lagou•Longda Jiang•Anna Ulrich•Liudmila Zudina•Karla Sofia Gutiérrez González等 96 人
Nature Genetics
2023
•2023/9/7
•Vol.55 No.9 p.1448-1461
Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on ‘around the clock’ glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstand...
DiseasesGenetics
10.1038/S41588-023-01462-3
ISSN:1061-4036
A summary-statistics-based approach to examine the role of serotonin transporter promoter tandem repeat polymorphism in psychiatric phenotypes
Majumdar Arunabha•Patel Preksha•Pasaniuc Bogdan•Ophoff Roel A.
European Journal Of Human Genetics
2021
•2021/12/23
•00 p.1-8
In genetic studies of psychiatric disorders in the pre-genome-wide association study (GWAS) era, one of the most commonly studied loci is the serotonin transporter (SLC6A4) promoter polymorphism, a 43-base-pair insertion/deletion polymorphism in the promoter region (5-HTTLPR). The genetic associatio...
Behavioural geneticsGenetic association study
10.1038/S41431-021-00996-6
ISSN:1018-4813
Genome-wide discovery for biomarkers using quantile regression at biobank scale
Chen Wang•Tianying Wang•Krzysztof Kiryluk•Ying Wei•Hugues Aschard等 6 人
Nature Communications
2024
•2024/7/31
•Vol.15 No.1 p.1-13
Genome-wide association studies (GWAS) for biomarkers important for clinical phenotypes can lead to clinically relevant discoveries. Conventional GWAS for quantitative traits are based on simplified regression models modeling the conditional mean of a phenotype as a linear function of genotype. We d...
Diagnostic markersGenome-wide association studiesStatistical methods
10.1038/S41467-024-50726-X
ISSN:2041-1723
Smoking, education level and excess premature deaths in the USA
Xuyang Tang•Eo Rin Cho•Patrick Brown•Kenneth E. Warner•Prabhat Jha
Nature Health
2026
•2026/7/10
•00 p.1-12
Adult survival among non-Hispanic white (‘white’) people in the USA has stagnated in recent decades, driven by rising mortality among adults with low educational attainment. We examined national mortality and population data to quantify the contributions of smoking-attributable diseases and selected...
EpidemiologyRisk factors
10.1038/S44360-026-00153-7
ISSN:3005-0693
Multi-ancestry sequencing-based genome-wide association study of C-reactive protein in 513,273 genomes
Hongru Li•Jingyi Zhao•Jinglan Dai•Dongfang You•Yang Zhao等 8 人
Nature Communications
2025
•2025/4/24
•Vol.16 No.1 p.1-11
C-reactive protein (CRP) serves as a pivotal marker of systemic inflammation, yet its genetic architecture has predominantly been explored within European populations. Our multi-ancestry sequencing-based genome-wide association study (seqGWAS) meta-analysis encompasses 447,369 Europeans, 10,389 Afri...
Diagnostic markersGenome-wide association studiesImmunogenetics
10.1038/S41467-025-59155-W
ISSN:2041-1723
A machine learning-derived polygenic risk score reveals that healthy lifestyle counteracts obesity-related mortality
Lushan Xiao•Shengxing Liang•Lin Zeng•Shumin Cai•Jiaren Wang等 15 人
Npj Digital Medicine
2026
•2026/1/6
•Vol.9 No.1 p.720
Obesity is influenced by genetic predisposition and lifestyle. The associations among genetic susceptibility to obesity, lifestyle, and all-cause mortality remain unexplored. Our goal is to develop and validate a machine learning model to assess the genetic risk of obesity and examine its associatio...
DiseasesGeneticsHealth careMedical researchRisk factors
10.1038/S41746-025-02314-6
ISSN:2398-6352
The brain structure, immunometabolic and genetic mechanisms underlying the association between lifestyle and depression
Yujie Zhao•Liu Yang•Barbara J. Sahakian•Christelle Langley•Wei Zhang等 13 人
Nature Mental Health
2023
•2023/9/11
•00 p.1-15
Lifestyle factors have been acknowledged to be modifiable targets that can be used to counter the increasing prevalence of depression. This study aims to investigate combining an extensive range of lifestyle factors, including alcohol consumption, diet, physical activity, sleep, smoking, sedentary b...
Brain imagingDepressionLifestyle modificationRisk factors
10.1038/S44220-023-00120-1
ISSN:2731-6076
The DNA virome varies with human genes and environments
Nolan Kamitaki•David Tang•Steven A. McCarroll•Po-Ru Loh
Nature
2026
•2026/3/25
•00 p.1-11
Many viruses have adapted to persist in infected humans for life1,2. Variable host control of their ongoing abundance (viral load) can lead to clearance or disease3–5. Here we analysed the viral DNA load of 31 common viruses in human blood and saliva using whole-genome sequencing data from UK Bioban...
Genome-wide association studiesRisk factorsTumour virus infectionsVirus–host interactions
10.1038/S41586-026-10288-Y
ISSN:0028-0836
Human and bacterial genetic variation shape oral microbiomes and health
Nolan Kamitaki•Robert E. Handsaker•Margaux L. A. Hujoel•Ronen E. Mukamel•Christina L. Usher等 7 人
Nature
2026
•2026/1/28
•Vol.651 No.8105 p.429-439
Human genetic variation influences all aspects of our biology, including the oral cavity1–3, through which nutrients and microbes enter the body. Yet it is largely unknown which human genetic variants shape a person’s oral microbiome and potentially promote its dysbiosis3–5. We characterized the ora...
Bacterial geneticsDental cariesGenome-wide association studies
10.1038/S41586-025-10037-7
ISSN:0028-0836
Mapping and annotating genomic loci to prioritize genes and implicate distinct polygenic adaptations for skin color
Beomsu Kim•Dan Say Kim•Joong-Gon Shin•Sangseob Leem•Minyoung Cho等 15 人
Nature Communications
2024
•2024/6/7
•Vol.15 No.1 p.1-16
Evidence for adaptation of human skin color to regional ultraviolet radiation suggests shared and distinct genetic variants across populations. However, skin color evolution and genetics in East Asians are understudied. We quantified skin color in 48,433 East Asians using image analysis and identifi...
Evolutionary geneticsGenetic variationGenome-wide association studies
10.1038/S41467-024-49031-4
ISSN:2041-1723
The association between patterns of exposure to adverse life events and the risk of chronic kidney disease: a prospective cohort study of 140,997 individuals
Chunyang Li•Jie Chen•Yilong Chen•Chao Zhang•Huazhen Yang等 9 人
Translational Psychiatry
2024
•2024/10/7
•Vol.14 No.1 p.1-12
Exposure to adverse life events is linked to somatic disorders. The study aims to evaluate the association between adverse events at varying life stages and the risk of chronic kidney disease (CKD), a condition affecting about 10% population worldwide. This prospective cohort study included 140,997 ...
DiseasesGeneticsPsychology
10.1038/S41398-024-03114-4
ISSN:2158-3188
Rare coding variants in CHRNB2 reduce the likelihood of smoking
Veera M. Rajagopal•Kyoko Watanabe•Joelle Mbatchou•Ariane Ayer•Peter Quon等 40 人
Nature Genetics
2023
•2023/6/12
•00 p.1-11
Human genetic studies of smoking behavior have been thus far largely limited to common variants. Studying rare coding variants has the potential to identify drug targets. We performed an exome-wide association study of smoking phenotypes in up to 749,459 individuals and discovered a protective assoc...
Behavioural geneticsDrug discoveryPopulation genetics
10.1038/S41588-023-01417-8
ISSN:1061-4036
A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
Seviiri Mathias•Law Matthew H.•Ong Jue-Sheng•Gharahkhani Puya•Fontanillas Pierre等 8 人
Nature Communications
2022
•2022/12/10
•Vol.13 No.1 p.1-14
Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the Uni...
Cancer geneticsGenome-wide association studies
10.1038/S41467-022-35345-8
ISSN:2041-1723
Mapping multimorbidity progression among 190 diseases
Shasha Han•Sairan Li•Yunhaonan Yang•Lihong Liu•Libing Ma等 13 人
Communications Medicine
2024
•2024/7/11
•Vol.4 No.1 p.1-11
Current clustering of multimorbidity based on the frequency of common disease combinations is inadequate. We estimated the causal relationships among prevalent diseases and mapped out the clusters of multimorbidity progression among them. In this cohort study, we examined the progression of multimor...
DiseasesEpidemiologyPublic health
10.1038/S43856-024-00563-2
ISSN:2730-664X
Associations of autozygosity with a broad range of human phenotypes
David W Clark•Yukinori Okada•Kristjan H S Moore•Dan Mason•Nicola Pirastu等 436 人
Nature Communications
2019
•2019/10/31
•Vol.10 No.1 p.1-17
In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confoundi...
ConsanguinityGenetic association studyGenetic markersInbreeding
10.1038/S41467-019-12283-6
ISSN:2041-1723
Characterisation of the SMN1/2 locus using a highly specific variant caller on whole-genome sequence data from 500,000 individuals
Timothy S. Hall•Robin N. Beaumont•James Fasham•Emma L. Baple•Leigh Jackson等 7 人
European Journal Of Human Genetics
2026
•2026/7/2
•00 p.1-7
Spinal muscular atrophy (SMA) is a rare autosomal recessive condition caused by biallelic loss of the SMN1 gene that results in severe lower motor neuron degeneration in childhood. Targeted pre-symptomatic treatments have been shown to dramatically improve outcomes, supporting the inclusion of SMA i...
GeneticsGenomics
10.1038/S41431-026-02175-X
ISSN:1018-4813
A scalable variational inference approach for increased mixed-model association power
Hrushikesh Loya•Georgios Kalantzis•Fergus Cooper•Pier Francesco Palamara
Nature Genetics
2025
•2025/1/9
•00 p.1-8
The rapid growth of modern biobanks is creating new opportunities for large-scale genome-wide association studies (GWASs) and the analysis of complex traits. However, performing GWASs on millions of samples often leads to trade-offs between computational efficiency and statistical power, reducing th...
Genome-wide association studiesSoftware
10.1038/S41588-024-02044-7
ISSN:1061-4036
Exome-wide screening identifies novel rare risk variants for major depression disorder
Cheng Shiqiang•Cheng Bolun•Liu Li•Yang Xuena•Meng Peilin等 15 人
Molecular Psychiatry
2022
•2022/4/1
•00 p.1-6
Despite thousands of common genetic loci of major depression disorders (MDD) have been identified by GWAS to date, a large proportion of genetic variation predisposing to MDD remains unaccounted for. By utilizing the newly released UK Biobank 200,643 exome dataset, we conducted an exome-wide associa...
DepressionGenetics
10.1038/S41380-022-01536-4
ISSN:1359-4184
Maternal aging increases offspring adult body size via transmission of donut-shaped mitochondria
Runshuai Zhang•Jinan Fang•Ting Qi•Shihao Zhu•Luxia Yao等 16 人
Cell Research
2023
•2023/7/27
•00 p.1-14
Maternal age at childbearing has continued to increase in recent decades. However, whether and how it influences offspring adult traits are largely unknown. Here, using adult body size as the primary readout, we reveal that maternal rather than paternal age has an evolutionarily conserved effect on ...
AgeingEnergy metabolism
10.1038/S41422-023-00854-8
ISSN:1748-7838
Whole-genome sequencing analysis of anthropometric traits in 672,976 individuals reveals convergence between rare and common genetic associations
Gareth Hawkes•Harrison I. W. Wright•Robin N. Beaumont•Kartik Chundru•Aimee Hanson等 12 人
Nature Communications
2026
•2026/2/6
•Vol.17 No.1 p.24320
GWAS have generally focused on common variants from genotyping arrays or rare protein-coding variants from exome sequencing. Here, we use whole-genome sequencing data to evaluate the contribution to and architecture of rare non-coding variants for three commonly studied anthropometric traits: height...
Gene regulationGenome-wide association studiesQuantitative trait loci
10.1038/S41467-026-69208-3
ISSN:2041-1723
Integrated multi-omics identifies distinct macrophage alterations during progression of metabolic dysfunction-associated steatohepatitis
Markus Boesch•Seray Anak•Dania El Abyad•Tessa Ostyn•Asier Antoranz等 48 人
Nature Genetics
2026
•2026/5/18
•00 p.1-13
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition impacting over 30% population, yet the dynamic changes in macrophage composition from steatosis to steatohepatitis (metabolic dysfunction-associated steatohepatitis, MASH) remain unclear. Here, by integrating sin...
Liver diseasesMetabolic disordersMolecular biology
10.1038/S41588-026-02600-3
ISSN:1061-4036
Prospective study of bipolar disorder and neurodegenerative diseases
Xinming Xu•Yaqi Li•Hanyu Lu•Han Wang•Yi Guo等 10 人
Npj Parkinson's Disease
2024
•2024/10/3
•Vol.10 No.1 p.1-8
Bipolar disorder (BD) is linked to an increased risk of neurodegenerative diseases such as dementia and Parkinson disease (PD), yet several uncertainties still remain and the extent to which the associations could be explained by BD-related medications (antipsychotics, lithium, and antiepileptics) w...
EpidemiologyNeurodegenerative diseases
10.1038/S41531-024-00794-Z
ISSN:2373-8057
Saturation genome editing of DDX3X clarifies pathogenicity of germline and somatic variation
Elizabeth J. Radford•Hong-Kee Tan•Malin H. L. Andersson•James D. Stephenson•Eugene J. Gardner等 19 人
Nature Communications
2023
•2023/12/6
•Vol.14 No.1 p.1-17
Loss-of-function of DDX3X is a leading cause of neurodevelopmental disorders (NDD) in females. DDX3X is also a somatically mutated cancer driver gene proposed to have tumour promoting and suppressing effects. We perform saturation genome editing of DDX3X, testing in vitro the functional impact of 12...
Cancer geneticsMutagenesisMutationNeurodevelopmental disorders
10.1038/S41467-023-43041-4
ISSN:2041-1723
Robust Mendelian randomization in the presence of residual population stratification, batch effects and horizontal pleiotropy
Cinelli Carlos•LaPierre Nathan•Hill Brian L.•Sankararaman Sriram•Eskin Eleazar
Nature Communications
2022
•2022/3/1
•Vol.13 No.1 p.1-13
Mendelian Randomization (MR) studies are threatened by population stratification, batch effects, and horizontal pleiotropy. Although a variety of methods have been proposed to mitigate those problems, residual biases may still remain, leading to highly statistically significant false positives in la...
GeneticsRisk factors
10.1038/S41467-022-28553-9
ISSN:2041-1723
Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease
Yanhua Chen•Xiaomeng Du•Annapurna Kuppa•Mary F. Feitosa•Lawrence F. Bielak等 37 人
Nature Genetics
2023
•2023/9/14
•00 p.1-11
Nonalcoholic fatty liver disease (NAFLD) is common and partially heritable and has no effective treatments. We carried out a genome-wide association study (GWAS) meta-analysis of imaging (n = 66,814) and diagnostic code (3,584 cases versus 621,081 controls) measured NAFLD across diverse ancestries. ...
GeneticsLiver diseases
10.1038/S41588-023-01497-6
ISSN:1061-4036
Obesity due to MC4R deficiency is associated with reduced cholesterol, triglycerides and cardiovascular disease risk
Stefanie Zorn•Rebecca Bounds•Alice Williamson•Katherine Lawler•Ruth Hanssen等 16 人
Nature Medicine
2025
•2025/10/16
•00 p.1-9
Obesity causes dyslipidemia and is a major risk factor for cardiovascular disease. However, the mechanisms coupling weight gain and lipid metabolism are poorly understood. Brain melanocortin 4 receptors (MC4Rs) regulate body weight and lipid metabolism in mice, but the relevance of these findings to...
Endocrine system and metabolic diseasesGenetic association studyMetabolism
10.1038/S41591-025-03976-1
ISSN:1078-8956
Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma
Joel T. Rämö•Bryan R. Gorman•Lu-Chen Weng•Sean J. Jurgens•Panisa Singhanetr等 31 人
Nature Communications
2025
•2025/5/3
•Vol.16 No.1 p.1-13
Central serous chorioretinopathy is an eye disease characterized by fluid buildup under the central retina whose etiology is not well understood. Abnormal choroidal veins in central serous chorioretinopathy patients have been shown to have similarities with varicose veins. To identify potential mech...
Disease geneticsEye diseasesGenome-wide association studiesVascular diseases
10.1038/S41467-025-58686-6
ISSN:2041-1723
Circulating fatty acids and risk of hepatocellular carcinoma and chronic liver disease mortality in the UK Biobank
Zhening Liu•Hangkai Huang•Jiarong Xie•Yingying Xu•Chengfu Xu
Nature Communications
2024
•2024/5/2
•Vol.15 No.1 p.1-10
Nuclear magnetic resonance (NMR)-based plasma fatty acids are objective biomarkers of many diseases. Herein, we aim to explore the associations of NMR-based plasma fatty acids with the risk of hepatocellular carcinoma (HCC) and chronic liver disease (CLD) mortality in 252,398 UK Biobank participants...
EpidemiologyLiver diseasesPredictive markers
10.1038/S41467-024-47960-8
ISSN:2041-1723
Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes
Akbari Parsa•Sosina Olukayode A.•Bovijn Jonas•Landheer Karl•Nielsen Jonas B.等 60 人
Nature Communications
2022
•2022/8/23
•Vol.13 No.1 p.1-17
Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide s...
Genetic association studyObesityPersonalized medicine
10.1038/S41467-022-32398-7
ISSN:2041-1723
Genetically adjusted PSA levels for prostate cancer screening
Linda Kachuri•Thomas J. Hoffmann•Yu Jiang•Sonja I. Berndt•John P. Shelley等 23 人
Nature Medicine
2023
•2023/6/1
•00 p.1-12
Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utilit...
Cancer geneticsCancer screeningDiagnostic markersProstate cancer
10.1038/S41591-023-02277-9
ISSN:1078-8956
The genetic architecture of fornix white matter microstructure and their involvement in neuropsychiatric disorders
Ya-Nan Ou•Yi-Jun Ge•Bang-Sheng Wu•Yi Zhang•Yu-Chao Jiang等 11 人
Translational Psychiatry
2023
•2023/5/26
•Vol.13 No.1 p.1-12
The fornix is a white matter bundle located in the center of the hippocampaldiencephalic limbic circuit that controls memory and executive functions, yet its genetic architectures and involvement in brain disorders remain largely unknown. We carried out a genome-wide association analysis of 30,832 U...
DiseasesNeuroscience
10.1038/S41398-023-02475-6
ISSN:2158-3188
No phenotypic or genotypic evidence for a link between sleep duration and brain atrophy
Anders M. Fjell•Øystein Sørensen•Yunpeng Wang•Inge K. Amlien•William F. C. Baaré等 24 人
Nature Human Behaviour
2023
•2023/10/5
•00 p.1-15
Short sleep is held to cause poorer brain health, but is short sleep associated with higher rates of brain structural decline? Analysing 8,153 longitudinal MRIs from 3,893 healthy adults, we found no evidence for an association between sleep duration and brain atrophy. In contrast, cross-sectional a...
Neural ageingSleep disorders
10.1038/S41562-023-01707-5
ISSN:2397-3374
Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease
Satoshi Yoshiji•Tianyuan Lu•Guillaume Butler-Laporte•Julia Carrasco-Zanini-Sanchez•Chen-Yang Su等 29 人
Nature Genetics
2025
•2025/1/24
•Vol.57 No.2 p.345-357
Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke...
Cardiovascular diseasesDrug discoveryObesityPersonalized medicine
10.1038/S41588-024-02052-7
ISSN:1061-4036
Sex-specific genetic architecture of blood pressure
Min-Lee Yang•Chang Xu•Trisha Gupte•Thomas J. Hoffmann•Carlos Iribarren等 7 人
Nature Medicine
2024
•2024/3/8
•00 p.1-11
The genetic and genomic basis of sex differences in blood pressure (BP) traits remain unstudied at scale. Here, we conducted sex-stratified and combined-sex genome-wide association studies of BP traits using the UK Biobank resource, identifying 1,346 previously reported and 29 new BP trait-associate...
Genetics researchGenome-wide association studies
10.1038/S41591-024-02858-2
ISSN:1078-8956
The role of genetic predisposition in cardiovascular risk after cancer diagnosis: a matched cohort study of the UK Biobank
Yang Huazhen•Zeng Yu•Chen Wenwen•Sun Yajing•Hu Yao等 11 人
British Journal Of Cancer
2022
•2022/8/24
•Vol.127 No.9 p.1650-1659
Evidence is scarce regarding the potential modifying role of disease susceptibility on the association between a prior cancer diagnosis and cardiovascular disease (CVD). We conducted a matched cohort study of UK Biobank including 78,860 individuals with a cancer diagnosis between January 1997 and Ja...
EpidemiologyHealth care
10.1038/S41416-022-01935-Y
ISSN:0007-0920
A global analysis of dairy consumption and incident cardiovascular disease
Pan Zhuang•Xiaohui Liu•Yin Li•Yang Ao•Yuqi Wu等 15 人
Nature Communications
2025
•2025/1/6
•Vol.16 No.1 p.1-13
The role of dairy products in cardiovascular disease (CVD) prevention remains controversial. This study investigates the association between dairy consumption and CVD incidence using data from the China Kadoorie Biobank and the UK Biobank, complemented by an updated meta-analysis. Among Chinese part...
Cardiovascular diseasesEpidemiologyPreventive medicine
10.1038/S41467-024-55585-0
ISSN:2041-1723
Tinnitus risk factors and its evolution over time
Lise Hobeika•Matt Fillingim•Christophe Tanguay-Sabourin•Mathieu Roy•Alain Londero等 7 人
Nature Communications
2025
•2025/5/7
•Vol.16 No.1 p.1-11
Subjective tinnitus is an auditory percept unrelated to external sounds, for which the limited understanding of its risk factors complicates the prevention and management. In this study, we train two distinct machine learning models to predict tinnitus presence (how often individuals perceive tinnit...
PsychologyRisk factors
10.1038/S41467-025-59445-3
ISSN:2041-1723
The effect of X-linked dosage compensation on complex trait variation
Julia Sidorenko•Irfahan Kassam•Kathryn E. Kemper•Jian Zeng•Luke R. Lloyd-Jones等 12 人
Nature Communications
2019
•2019/7/8
•Vol.10 No.1 p.1-11
Quantitative genetics theory predicts that X-chromosome dosage compensation (DC) will have a detectable effect on the amount of genetic and therefore phenotypic trait variances at associated loci in males and females. Here, we systematically examine the role of DC in humans in 20 complex traits in a...
Dosage compensationGene expressionGenomicsHeritable quantitative trait
10.1038/S41467-019-10598-Y
ISSN:2041-1723
Liability threshold modeling of case–control status and family history of disease increases association power
Margaux L. A. Hujoel•Steven Gazal•Po-Ru Loh•Nick Patterson•Alkes L. Price
Nature Genetics
2020
•2020/4/20
•Vol.52 No.5 p.541-547
Family history of disease can provide valuable information in case–control association studies, but it is currently unclear how to best combine case–control status and family history of disease. We developed an association method based on posterior mean genetic liabilities under a liability threshol...
Genetic association studyGenome-wide association studies
10.1038/S41588-020-0613-6
ISSN:1061-4036
Accurate prediction of disease-risk factors from volumetric medical scans by a deep vision model pre-trained with 2D scans
Oren Avram•Berkin Durmus•Nadav Rakocz•Giulia Corradetti•Ulzee An等 33 人
Nature Biomedical Engineering
2024
•2024/10/1
•00 p.1-14
The application of machine learning to tasks involving volumetric biomedical imaging is constrained by the limited availability of annotated datasets of three-dimensional (3D) scans for model training. Here we report a deep-learning model pre-trained on 2D scans (for which annotated data are relativ...
BiomarkersBiomedical engineeringDiagnosisThree-dimensional imaging
10.1038/S41551-024-01257-9
ISSN:2157-846X
Association of pre-existing depression and anxiety with Omicron variant infection
Huazhen Yang•Lei Yang•Wenwen Chen•Yu Zeng•Yanan Zhang等 16 人
Molecular Psychiatry
2024
•2024/5/16
•00 p.1-9
Pre-existing psychiatric disorders were linked to an increased susceptibility to COVID-19 during the initial outbreak of the pandemic, while evidence during Omicron prevalence is lacking. Leveraging data from two prospective cohorts in China, we identified incident Omicron infections between January...
DiseasesPsychiatric disorders
10.1038/S41380-024-02594-6
ISSN:1359-4184
Proteomic signatures improve risk prediction for common and rare diseases
Julia Carrasco-Zanini•Maik Pietzner•Jonathan Davitte•Praveen Surendran•Damien C. Croteau-Chonka等 22 人
Nature Medicine
2024
•2024/7/22
•00 p.1-10
For many diseases there are delays in diagnosis due to a lack of objective biomarkers for disease onset. Here, in 41,931 individuals from the United Kingdom Biobank Pharma Proteomics Project, we integrated measurements of ~3,000 plasma proteins with clinical information to derive sparse prediction m...
Disease preventionPredictive markersRisk factors
10.1038/S41591-024-03142-Z
ISSN:1078-8956
A genome-first study of sex chromosome aneuploidies provides evidence of Y chromosome dosage effects on autism risk
Alexander S. F. Berry•Brenda M. Finucane•Scott M. Myers•Lauren K. Walsh•John M. Seibert等 8 人
Nature Communications
2024
•2024/10/15
•Vol.15 No.1 p.1-11
A female protective effect has long been postulated as the primary explanation for the four-fold increase of autism spectrum disorder (ASD) diagnoses in males versus females. However, genetic and epidemiological investigations of this hypothesis have so far failed to explain the large difference in ...
Autism spectrum disordersMedical genomicsRisk factors
10.1038/S41467-024-53211-7
ISSN:2041-1723
Traumatic events during childhood and its risks to substance use in adulthood: an observational and genome-wide by environment interaction study in UK Biobank
Cheng Shiqiang•Wen Yan•Liu Li•Cheng Bolun•Liang Chujun等 11 人
Translational Psychiatry
2021
•2021/8/20
•Vol.11 No.1 p.1-6
We aimed to explore the underlying genetic mechanisms of traumatic events during childhood affecting the risks of adult substance use in present study. Using UK Biobank cohort, linear regression model was first applied to assess the relationships between cigarette smoking and alcohol drinking in adu...
AddictionClinical genetics
10.1038/S41398-021-01557-7
ISSN:2158-3188
BrainParc: unified lifespan brain parcellation from structural magnetic resonance images
Jiameng Liu•Feihong Liu•Kaicong Sun•Zhiming Cui•Tianyang Sun等 16 人
Nature Computational Science
2026
•2026/3/11
•00 p.1-15
Accurate brain parcellation from structural MRI across the human lifespan is essential for advancing neuroimaging and neuroscience studies. However, existing methods often struggle to generalize owing to intensity and contrast variations across brain maturation, aging and differences in MRI acquisit...
Brain imagingComputational neuroscienceMagnetic resonance imaging
10.1038/S43588-026-00963-5
ISSN:2662-8457
Analyses of biomarker traits in diverse UK biobank participants identify associations missed by European-centric analysis strategies
Sun Quan•Graff Misa•Rowland Bryce•Wen Jia•Huang Le等 19 人
Journal Of Human Genetics
2021
•2021/8/11
•00 p.1-7
Despite the dramatic underrepresentation of non-European populations in human genetics studies, researchers continue to exclude participants of non-European ancestry, as well as variants rare in European populations, even when these data are available. This practice perpetuates existing research dis...
Genetic markersGenome-wide association studiesPredictive markers
10.1038/S10038-021-00968-0
ISSN:1434-5161
Eye-brain connections revealed by multimodal retinal and brain imaging genetics
Bingxin Zhao•Yujue Li•Zirui Fan•Zhenyi Wu•Juan Shu等 18 人
Nature Communications
2024
•2024/7/18
•Vol.15 No.1 p.1-19
The retina, an anatomical extension of the brain, forms physiological connections with the visual cortex of the brain. Although retinal structures offer a unique opportunity to assess brain disorders, their relationship to brain structure and function is not well understood. In this study, we conduc...
GeneticsGenome-wide association studiesNeuroscience
10.1038/S41467-024-50309-W
ISSN:2041-1723
Calibrated prediction intervals for polygenic scores across diverse contexts
Kangcheng Hou•Ziqi Xu•Yi Ding•Ravi Mandla•Zhuozheng Shi等 8 人
Nature Genetics
2024
•2024/6/17
•00 p.1-11
Polygenic scores (PGS) have emerged as the tool of choice for genomic prediction in a wide range of fields. We show that PGS performance varies broadly across contexts and biobanks. Contexts such as age, sex and income can impact PGS accuracy with similar magnitudes as genetic ancestry. Here we intr...
Computational biology and bioinformaticsPopulation genetics
10.1038/S41588-024-01792-W
ISSN:1061-4036
Deriving novel atrial fibrillation phenotypes using a tree-based artificial intelligence-enhanced electrocardiography approach
Mehak Gurnani•Konstantinos Patlatzoglou•Joseph Barker•Libor Pastika•Boroumand Zeidaabadi等 16 人
Npj Digital Medicine
2025
•2025/12/4
0Atrial fibrillation (AF) is classically categorised by arrhythmia duration, but these subtypes have limitations in capturing mechanistic and prognostic diversity. A variational autoencoder, trained on >1.1M ECGs, extracted representative features, filtered for an AF cohort of 20,291 unique patien...
Atrial fibrillationMachine learning
10.1038/S41746-025-02159-Z
ISSN:2398-6352
Germline-somatic JAK2 interactions are associated with clonal expansion in myelofibrosis
Brown Derek W.•Zhou Weiyin•Wang Youjin•Jones Kristine•Luo Wen等 31 人
Nature Communications
2022
•2022/9/8
•Vol.13 No.1 p.1-11
Myelofibrosis is a rare myeloproliferative neoplasm (MPN) with high risk for progression to acute myeloid leukemia. Our integrated genomic analysis of up to 933 myelofibrosis cases identifies 6 germline susceptibility loci, 4 of which overlap with previously identified MPN loci. Virtual karyotyping ...
Cancer geneticsCancer genomicsHaematopoietic stem cellsMutationMyeloproliferative disease
10.1038/S41467-022-32986-7
ISSN:2041-1723
The shared genetic architecture and evolution of human language and musical rhythm
Gökberk Alagöz•Else Eising•Yasmina Mekki•Giacomo Bignardi•Pierre Fontanillas等 10 人
Nature Human Behaviour
2024
•2024/11/21
•00 p.1-15
This study aimed to test theoretical predictions over biological underpinnings of previously documented phenotypic correlations between human language-related and musical rhythm traits. Here, after identifying significant genetic correlations between rhythm, dyslexia and various language-related tra...
Evolutionary geneticsGenome-wide association studies
10.1038/S41562-024-02051-Y
ISSN:2397-3374
A versatile, fast and unbiased method for estimation of gene-by-environment interaction effects on biobank-scale datasets
Matteo Di Scipio•Mohammad Khan•Shihong Mao•Michael Chong•Conor Judge等 13 人
Nature Communications
2023
•2023/8/25
•Vol.14 No.1 p.1-15
Identification of gene-by-environment interactions (GxE) is crucial to understand the interplay of environmental effects on complex traits. However, current methods evaluating GxE on biobank-scale datasets have limitations. We introduce MonsterLM, a multiple linear regression method that does not re...
EpidemiologyGenetics researchPredictive markersQuantitative trait
10.1038/S41467-023-40913-7
ISSN:2041-1723
A large-scale genome-wide association meta-analysis for nevus count provides direct insights into the genetics of melanoma
G. J. M. Shanika R. Jayasinghe•Gu Zhu•Nirmala Pandeya•Catherine M. Olsen•Nicholas G. Martin等 30 人
Nature Communications
2026
•2026/3/10
0A greater understanding of the biology of nevi will provide insights into the etiology of melanoma. Our large-scale meta-analysis of 14 nevus genome-wide association studies (GWAS) includes 85,965 individuals of European ancestry. We identify 29 nevus-associated loci (p < 5 × 10-8), of which 24 h...
Genome-wide association studiesMelanoma
10.1038/S41467-026-70368-5
ISSN:2041-1723
Genetic drivers and cellular selection of female mosaic X chromosome loss
Aoxing Liu•Giulio Genovese•Yajie Zhao•Matti Pirinen•Seyedeh M. Zekavat等 41 人
Nature
2024
•2024/6/12
•00 p.1-8
Mosaic loss of the X chromosome (mLOX) is the most common clonal somatic alteration in leukocytes of female individuals1,2, but little is known about its genetic determinants or phenotypic consequences. Here, to address this, we used data from 883,574 female participants across 8 biobanks; 12% ...
BiomarkersGenetic variationGenome-wide association studiesMolecular evolution
10.1038/S41586-024-07533-7
ISSN:0028-0836
Inference of chronic obstructive pulmonary disease with deep learning on raw spirograms identifies new genetic loci and improves risk models
Cosentino Justin•Behsaz Babak•Alipanahi Babak•McCaw Zachary R.•Hill Davin等 12 人
Nature Genetics
2023
•2023/4/17
•00 p.1-9
Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is highly heritable. While COPD is clinically defined by applying thresholds to summary measures of lung function, a quantitative liability score has more power to identify genetic signals. Here we train a deep...
Genome-wide association studiesPopulation genetics
10.1038/S41588-023-01372-4
ISSN:1061-4036
Imaging-based organ-specific aging clock predicts human diseases and mortality
Peng Ren•Wenjing Su•Jia You•Ying Liang•Weikang Gong等 14 人
Npj Digital Medicine
2026
•2026/2/25
•Vol.9 No.1 p.2780
Organ-specific aging clocks hold great potential in reflecting organ health. In vivo imaging is inherently organ-specific and delineates structural and functional characteristics more objectively. However, there is no systematic evaluation of imaging-based aging clocks. We utilized 1777 imaging-deri...
BiomarkersDiseasesHealth careMedical research
10.1038/S41746-026-02488-7
ISSN:2398-6352
Adapting the BOADICEA breast and ovarian cancer risk models for the ethnically diverse UK population
Lorenzo Ficorella•Xin Yang•Nasim Mavaddat•Tim Carver•Hend Hassan等 26 人
British Journal Of Cancer
2025
•2025/7/17
•00 p.1-12
BOADICEA is a widely used algorithm for predicting breast and ovarian cancer risks, using a combination of genetic and lifestyle, hormonal and reproductive risk factors. However, it has largely been developed using data from White/European individuals, limiting its applicability to other ethnicities...
Breast cancerCancer epidemiologyCancer screeningEpidemiologyOvarian cancer
10.1038/S41416-025-03117-Y
ISSN:0007-0920
Rare mutations in the complement regulatory gene CSMD1 are associated with male and female infertility
Arthur S. Lee•Jannette Rusch•Ana C. Lima•Abul Usmani•Ni Huang等 16 人
Nature Communications
2019
•2019/10/11
•Vol.10 No.1 p.1-16
Infertility in men and women is a complex genetic trait with shared biological bases between the sexes. Here, we perform a series of rare variant analyses across 73,185 women and men to identify genes that contribute to primary gonadal dysfunction. We report CSMD1, a complement regulatory protein on...
Genetic association studyInfertilityMenopauseStructural variation
10.1038/S41467-019-12522-W
ISSN:2041-1723
Body composition and mortality from middle to old age: a prospective cohort study from the UK Biobank
Sanchez-Lastra Miguel Adriano•Ding Ding•Dalene Knut Eirik•del Pozo Cruz Borja•Ekelund Ulf等 6 人
International Journal Of Obesity
2023
•2023/4/22
•00 p.1-8
How the association between adiposity and the risk of death changes with age, and which is the optimal level of adiposity to reduce mortality in older ages, is still not completely understood. We aimed to ascertain the age-specific risks of mortality associated with different measures of adiposity. ...
EndocrinologyRisk factors
10.1038/S41366-023-01314-4
ISSN:0307-0565
Genome-wide associations of structural variants with human traits through imputation from long-read assemblies
Wei-Yang Bai•Shuli Liu•Zhongqu Duan•Ji-Jian Yang•Jie Chen等 10 人
Nature Genetics
2026
•2026/5/20
•00 p.1-10
Structural variants (SVs) are a major type of genetic variation, yet their role in human traits remains largely uncharacterized, primarily due to challenges in genotyping them on a genome-wide scale in large cohorts. Here we identified 171,233 high-quality, genome-wide SVs from 482 haplotype-resolve...
Genome-wide association studiesGenomics
10.1038/S41588-026-02612-Z
ISSN:1061-4036
Missense variants in FRS3 affect body mass index in populations of diverse ancestries
Andrea B. Jonsdottir•Gardar Sveinbjornsson•Rosa B. Thorolfsdottir•Max Tamlander•Vinicius Tragante等 75 人
Nature Communications
2025
•2025/3/25
•Vol.16 No.1 p.1-16
Obesity is associated with adverse effects on health and quality of life. Improved understanding of its underlying pathophysiology is essential for developing counteractive measures. To search for sequence variants with large effects on BMI, we perform a multi-ancestry meta-analysis of 13 genome-wid...
Genome-wide association studiesObesityPopulation genetics
10.1038/S41467-025-57753-2
ISSN:2041-1723
Prodromal Parkinson’s disease and subsequent risk of Parkinson’s disease and mortality
Xiao Chen•Yaqi Li•Yun Shen•Michael A. Schwarzschild•Xiang Gao
Npj Parkinson's Disease
2025
•2025/1/9
•Vol.11 No.1 p.1-8
Association of prodromal Parkinson’s disease (PD) with risk of PD and risk of mortality in individuals with PD warrant investigation through large-scale prospective study. We included 501,475 participants without PD at baseline. Eight prodromal features were measured. Incident PD cases were identifi...
Neurological disordersParkinson's disease
10.1038/S41531-024-00863-3
ISSN:2373-8057
Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility
Maria Teresa Landi•D. Timothy Bishop•Stuart MacGregor•Mitchell J. Machiela•Alexander J. Stratigos等 143 人
Nature Genetics
2020
•2020/4/27
•Vol.52 No.5 p.494-504
Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10−8) loci with 68 independent single nucleotide polymorphisms. Ana...
Genome-wide association studiesMelanoma
10.1038/S41588-020-0611-8
ISSN:1061-4036
Unique genetic and risk-factor profiles in clusters of major depressive disorder-related multimorbidity trajectories
Andras Gezsi•Sandra Van der Auwera•Hannu Mäkinen•Nora Eszlari•Gabor Hullam等 21 人
Nature Communications
2024
•2024/8/21
•Vol.15 No.1 p.1-18
The heterogeneity and complexity of symptom presentation, comorbidities and genetic factors pose challenges to the identification of biological mechanisms underlying complex diseases. Current approaches used to identify biological subtypes of major depressive disorder (MDD) mainly focus on clinical ...
Data processingDepressionEpidemiologyGenetics researchGenome-wide association studies
10.1038/S41467-024-51467-7
ISSN:2041-1723
Neuroimaging endophenotypes reveal underlying mechanisms and genetic factors contributing to progression and development of four brain disorders
Junhao Wen•Ioanna Skampardoni•Ye Ella Tian•Zhijian Yang•Yuhan Cui等 17 人
Nature Biomedical Engineering
2025
•2025/6/6
•00 p.1-18
Recent work leveraging artificial intelligence has offered promise to dissect disease heterogeneity by identifying complex intermediate brain phenotypes, called dimensional neuroimaging endophenotypes (DNEs). We advance the argument that these DNEs capture the degree of expression of respective neur...
Genetic markersMachine learning
10.1038/S41551-025-01412-W
ISSN:2157-846X
Calibrated rare variant genetic risk scores for complex disease prediction using large exome sequence repositories
Lali Ricky•Chong Michael•Omidi Arghavan•Mohammadi-Shemirani Pedrum•Le Ann等 7 人
Nature Communications
2021
•2021/10/6
•Vol.12 No.1 p.1-15
Rare variants are collectively numerous and may underlie a considerable proportion of complex disease risk. However, identifying genuine rare variant associations is challenging due to small effect sizes, presence of technical artefacts, and heterogeneity in population structure. We hypothesize that...
Genetic predisposition to diseaseNext-generation sequencingRare variantsStatistical methods
10.1038/S41467-021-26114-0
ISSN:2041-1723
Improving fine-mapping by modeling infinitesimal effects
Ran Cui•Roy A. Elzur•Masahiro Kanai•Jacob C. Ulirsch•Omer Weissbrod等 9 人
Nature Genetics
2023
•2023/11/30
•00 p.1-8
Fine-mapping aims to identify causal genetic variants for phenotypes. Bayesian fine-mapping algorithms (for example, SuSiE, FINEMAP, ABF and COJO-ABF) are widely used, but assessing posterior probability calibration remains challenging in real data, where model misspecification probably exists, and ...
Computational biology and bioinformaticsGenome-wide association studies
10.1038/S41588-023-01597-3
ISSN:1061-4036
Using human genetics to understand the disease impacts of testosterone in men and women
Katherine S Ruth•Felix R Day•Jessica Tyrrell•Deborah J Thompson•Andrew R Wood等 13 人
Nature Medicine
2020
•2020/2/10
•Vol.26 No.2 p.252-258
Testosterone supplementation is commonly used for its effects on sexual function, bone health and body composition, yet its effects on disease outcomes are unknown. To better understand this, we identified genetic determinants of testosterone levels and related sex hormone traits in 425,097 UK Bioba...
DiabetesEndocrine cancerGenetics researchMetabolic syndromeMultihormonal system disorders
10.1038/S41591-020-0751-5
ISSN:1078-8956
Dynapenic obesity associated with incidence and progression trajectory of cardiometabolic diseases: a prospective cohort study
Nana Wang•Tianrun Wang•Xiaocan Jia•Zhixing Fan•Chaojun Yang等 11 人
International Journal Of Obesity
2025
•2025/7/3
•00 p.1-9
The impact of dynapenic obesity on the progression of cardiometabolic multimorbidity (CMM) remains poorly understood. This study aimed to explore the association between dynapenic obesity and cardiometabolic diseases (CMD) progression, as well as the mediating roles of C-reactive protein (CRP) and t...
Endocrine system and metabolic diseasesEpidemiology
10.1038/S41366-025-01831-4
ISSN:0307-0565
Polygenic prediction via Bayesian regression and continuous shrinkage priors
Tian Ge•Chia-Yen Chen•Yang Ni•Yen-Chen Anne Feng•Jordan W. Smoller
Nature Communications
2019
•2019/4/16
•Vol.10 No.1 p.1-10
Polygenic risk scores (PRS) have shown promise in predicting human complex traits and diseases. Here, we present PRS-CS, a polygenic prediction method that infers posterior effect sizes of single nucleotide polymorphisms (SNPs) using genome-wide association summary statistics and an external linkage...
Genetic association studyGenome-wide association studiesStatistical methodsStatistics
10.1038/S41467-019-09718-5
ISSN:2041-1723
An analysis of frailty and multimorbidity in 20,566 UK Biobank participants with type 2 diabetes
Hanlon Peter•Jani Bhautesh D.•Butterly Elaine•Nicholl Barbara•Lewsey Jim等 7 人
Communications Medicine
2021
•2021/8/27
•Vol.1 No.1 p.1-9
Frailty and multimorbidity are common in type 2 diabetes (T2D), including people <65 years. Guidelines recommend adjustment of treatment targets in people with frailty or multimorbidity. It is unclear how recommendations to adjust treatment targets in people with frailty or multimorbidity should be ...
EpidemiologyType 2 diabetes
10.1038/S43856-021-00029-9
ISSN:2730-664X
Genetic overlap between multivariate measures of human functional brain connectivity and psychiatric disorders
Daniel Roelfs•Dennis van der Meer•Dag Alnæs•Oleksandr Frei•Alexey A. Shadrin等 11 人
Nature Mental Health
2024
•2024/1/8
•00 p.1-11
Psychiatric disorders are complex, heritable and highly polygenic. Supported by findings of abnormalities in functional magnetic resonance imaging-based measures of brain connectivity, current theoretical and empirical accounts have conceptualized them as disorders of brain connectivity and dysfunct...
Genome-wide association studiesNeurosciencePsychiatric disorders
10.1038/S44220-023-00190-1
ISSN:2731-6076
GATK-gCNV enables the discovery of rare copy number variants from exome sequencing data
Mehrtash Babadi•Jack M. Fu•Samuel K. Lee•Andrey N. Smirnov•Laura D. Gauthier等 15 人
Nature Genetics
2023
•2023/8/21
•00 p.1-9
Copy number variants (CNVs) are major contributors to genetic diversity and disease. While standardized methods, such as the genome analysis toolkit (GATK), exist for detecting short variants, technical challenges have confounded uniform large-scale CNV analyses from whole-exome sequencing (WES) dat...
Genetics researchGenomics
10.1038/S41588-023-01449-0
ISSN:1061-4036
Reversal of proteomic aging with exercise—results from the UK biobank and a 12-week intervention study
Sindre Lee-Ødegård•M. Austin Argentieri•Frode Norheim•Christian Andre Drevon•Kåre Inge Birkeland
Npj Aging
2025
•2025/12/26
0Biological aging varies between individuals and may be influenced by health behaviors. Using data from 45,438 UK Biobank participants, we found that a higher proteomic aging score (ProtAgeGap) was linked to lower physical activity and increased risk of type 2 diabetes. The UK Biobank cohort included...
BiomarkersEndocrine system and metabolic diseasesTranslational research
10.1038/S41514-025-00318-W
ISSN:2731-6068
Genetic and environmental determinants of diastolic heart function
Thanaj Marjola•Mielke Johanna•McGurk Kathryn A.•Bai Wenjia•Savioli Nicolò等 17 人
Nature Cardiovascular Research
2022
•2022/4/13
•Vol.1 No.4 p.361-371
Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends on myocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processes and is predictive of health outcomes, but its ge...
Cardiovascular geneticsHeart failure
10.1038/S44161-022-00048-2
ISSN:2731-0590
Generating synthetic task-based brain fingerprints for population neuroscience using deep learning
Emin Serin•Kerstin Ritter•Gunter Schumann•Tobias Banaschewski•Andre Marquand等 6 人
Communications Biology
2025
•2025/11/14
•Vol.8 No.1 p.15720
Task-based functional magnetic resonance imaging (fMRI) reveals individual differences in neural correlates of cognition but faces scalability challenges due to cognitive demands, protocol variability, and limited task coverage in large datasets. Here, we propose DeepTaskGen, a deep-learning approac...
Computational neurosciencePredictive markers
10.1038/S42003-025-09158-6
ISSN:2399-3642
Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications
Rosalie B. T. M. Sterenborg•Inga Steinbrenner•Yong Li•Melissa N. Bujnis•Tatsuhiko Naito等 141 人
Nature Communications
2024
•2024/1/30
•Vol.15 No.1 p.1-18
To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total tr...
Genome-wide association studiesThyroid diseases
10.1038/S41467-024-44701-9
ISSN:2041-1723
SEAD reference panel with 22,134 haplotypes boosts rare variant imputation and genome-wide association analysis in Asian populations
Meng-Yuan Yang•Jia-Dong Zhong•Xin Li•Geng Tian•Wei-Yang Bai等 37 人
Nature Communications
2024
•2024/12/30
•Vol.15 No.1 p.1-14
Limited whole genome sequencing (WGS) studies in Asian populations result in a lack of representative reference panels, thus hindering the discovery of ancestry-specific variants. Here, we present the South and East Asian reference Database (SEAD) panel ( https://imputationserver.westlake.edu.cn/ ),...
Genome-wide association studiesRare variants
10.1038/S41467-024-55147-4
ISSN:2041-1723
The interaction of early life factors and depression-associated loci affecting the age at onset of the depression
Chen Yujing•Pan Chuyu•Cheng Shiqiang•Li Chun’e•Zhang Huijie等 15 人
Translational Psychiatry
2022
•2022/7/25
•Vol.12 No.1 p.1-8
Multiple previous studies explored the associations between early life factors and the age at onset of the depression. However, they only focused on the influence of environmental or genetic factors, without considering the interactions between them. Based on previous genome-wide association study (...
DepressionGenomicsScientific community
10.1038/S41398-022-02042-5
ISSN:2158-3188
Proteomic signatures of the APOE ε4 and APOE ε2 genetic variants and Alzheimer’s disease
Lina Lu•Alexa Pichet Binette•Ines Hristovska•Shorena Janelidze•Bart Smets等 17 人
Nature Aging
2026
•2026/5/15
•00 p.1-20
The APOE locus is the strongest genetic factor for Alzheimer’s disease, with ε4 increasing and ε2 decreasing risk, yet the basis of these opposing effects remains unclear. Here we performed a multicohort proteomic analysis across plasma and cerebrospinal fluid in GNPC, BioFINDER-2, ADNI, UK BioBank,...
AgeingAlzheimer's diseaseBiomarkersCognitive ageingGenetic association study
10.1038/S43587-026-01123-0
ISSN:2662-8465
Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts
Rebecca E. Graff•Taylor B. Cavazos•Khanh K. Thai•Linda Kachuri•Sara R. Rashkin等 21 人
Nature Communications
2021
•2021/2/12
•Vol.12 No.1 p.1-9
Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969...
Cancer epidemiologyCancer genetics
10.1038/S41467-021-21288-Z
ISSN:2041-1723
Associations between genetic loci, environment factors and mental disorders: a genome-wide survival analysis using the UK Biobank data
Meng Peilin•Ye Jing•Chu Xiaomeng•Cheng Bolun•Cheng Shiqiang等 9 人
Translational Psychiatry
2022
•2022/1/11
•Vol.12 No.1 p.1-7
It is well-accepted that both environment and genetic factors contribute to the development of mental disorders (MD). However, few genetic studies used time-to-event data analysis to identify the susceptibility genetic variants associated with MD and explore the role of environment factors in these ...
GenomicsMolecular neuroscience
10.1038/S41398-022-01782-8
ISSN:2158-3188
Age-dependent topic modeling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk
Xilin Jiang•Martin Jinye Zhang•Yidong Zhang•Arun Durvasula•Michael Inouye等 8 人
Nature Genetics
2023
•2023/10/9
•00 p.1-12
The analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) meth...
Computational biology and bioinformaticsGenomicsOutcomes researchPersonalized medicineSoftware
10.1038/S41588-023-01522-8
ISSN:1061-4036
A genome-wide association study identifies distinct variants associated with pulmonary function among European and African ancestries from the UK Biobank
Sinkala Musalula•Elsheikh Samar S. M.•Mbiyavanga Mamana•Cullinan Joshua•Mulder Nicola J.
Communications Biology
2023
•2023/1/14
•Vol.6 No.1 p.1-11
Pulmonary function is an indicator of well-being, and pulmonary pathologies are the third major cause of death worldwide. We analysed the UK Biobank genome-wide association summary statistics of pulmonary function for Europeans and individuals of recent African descent to identify variants associate...
Data integrationGenome-wide association studies
10.1038/S42003-023-04443-8
ISSN:2399-3642
Association of active commuting with incidence of depression and anxiety: prospective cohort study
Jingwen Fan•Xuesong Zhang•Xiaocan Jia•Zhixing Fan•Chaojun Yang等 10 人
Translational Psychiatry
2025
•2025/2/1
•Vol.15 No.1 p.1-9
Evidence is limited on the incidence of depression and anxiety in relation to active commuting. Our study aimed to explore their association and examine the mediating role of inflammatory. This study included 240,547 workers in the UK Biobank. The exposure variable was the mode of transport used to ...
DepressionPsychiatric disorders
10.1038/S41398-024-03219-W
ISSN:2158-3188
Patterns and drivers of 43,617 mosaic chromosomal alterations in blood
David Tang•Nolan Kamitaki•Ronen E. Mukamel•Simone Rubinacci•Po-Ru Loh
Nature Genetics
2026
•2026/5/19
•00 p.1-12
Clonal expansions of hematopoietic cells carrying mosaic chromosomal alterations (mCAs) are commonly detectable in elderly individuals. Here we studied 43,617 autosomal mCAs ascertained in 484,081 UK Biobank participants using new, high-resolution computational methods to analyze blood-derived, whol...
Genome-wide association studiesHaematological cancer
10.1038/S41588-026-02592-0
ISSN:1061-4036
Genetic variation associated with thyroid autoimmunity shapes the systemic immune response to PD-1 checkpoint blockade
Zia Khan•Christian Hammer•Jonathan Carroll•Flavia Di Nucci•Sergio Ley Acosta等 12 人
Nature Communications
2021
•2021/6/7
•Vol.12 No.1 p.1-12
Activation of systemic immune responses using PD-1 checkpoint inhibitors is an essential approach to cancer therapy. Yet, the extent of benefit relative to risk of immune related adverse events (irAE) varies widely among patients. Here, we study endocrine irAE from 7 clinical trials across 6 cancers...
Cancer geneticsGeneticsImmunotherapyRisk factors
10.1038/S41467-021-23661-4
ISSN:2041-1723
Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
Wang Zhe•Emmerich Andrew•Pillon Nicolas J.•Moore Tim•Hemerich Daiane等 218 人
Nature Genetics
2022
•2022/9/7
•Vol.54 No.9 p.1332-1344
Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associat...
Genetics researchGenome-wide association studiesTranslational research
10.1038/S41588-022-01165-1
ISSN:1061-4036
Accelerometer-measured physical activity, sedentary behavior, and incident neuropsychiatric diseases: a large prospective cohort study of 73411 participants
Jia-Yi Wu•Yu-Zhu Li•Dan-Dan Zhang•Pei-Yang Gao•Yan Fu等 10 人
Molecular Psychiatry
2025
•2025/9/20
•00 p.1-15
Physical activity and sedentary behavior are closely associated with neuropsychiatric diseases, while previous studies have mainly relied on self-reported data, which have been shown to be inconsistent with objectively measured metrics. Using data from 73,411 participants, objectively quantifying ph...
NeurosciencePsychiatric disorders
10.1038/S41380-025-03268-7
ISSN:1359-4184
Deep learning for detecting and early predicting chronic obstructive pulmonary disease from spirogram time series
Shuhao Mei•Xin Li•Yuxi Zhou•Jiahao Xu•Yong Zhang等 12 人
Npj Systems Biology And Applications
2025
•2025/2/15
•Vol.11 No.1 p.1-16
Chronic Obstructive Pulmonary Disease (COPD) is a chronic lung condition characterized by airflow obstruction. Current diagnostic methods primarily rely on identifying prominent features in spirometry (Volume-Flow time series) to detect COPD, but they are not adept at predicting future COPD risk bas...
Health careProgramming language
10.1038/S41540-025-00489-Y
ISSN:2056-7189
Higher habitual intakes of flavonoids and flavonoid-rich foods are associated with a lower incidence of type 2 diabetes in the UK Biobank cohort
Alysha S. Thompson•Amy Jennings•Nicola P. Bondonno•Anna Tresserra-Rimbau•Benjamin H. Parmenter等 9 人
Nutrition & Diabetes
2024
•2024/5/22
•Vol.14 No.1 p.1-10
To examine the associations of a diet high in flavonoid-rich foods, as reflected by a “Flavodiet Score” (FDS), the major individual food contributors to flavonoid intake, and flavonoid subclasses with type 2 diabetes (T2D) risk in the UK Biobank cohort. Flavonoid intakes were estimated from ≥2 dieta...
EpidemiologyLifestyle modificationRisk factorsType 2 diabetes
10.1038/S41387-024-00288-0
ISSN:2044-4052
The associations between diet-induced inflammation and health outcomes: a population-based phenome-wide association study
Weiwei Chen•Ke Liu•Xinzhe Jing•Yu Qian•Bin Liu等 10 人
Npj Science Of Food
2025
•2025/11/11
•Vol.9 No.1 p.2230
Evidence linking the dietary inflammatory index (DII) to health outcomes remains inconsistent and limited. This study assessed the associations between DII and 845 health outcomes (N = 78,390 to 207,832), identifying 133 outcomes significantly associated with DII after multiple comparison correction...
DiseasesGenomicsRisk factors
10.1038/S41538-025-00583-9
ISSN:2396-8370
Data-hugging shields proprietary AI models from research that could disprove them
Anish Karpurapu•Zhicheng Guo•Xiao Hu•Cynthia Rudin
Npj Artificial Intelligence
2026
•2026/4/17
•Vol.2 No.1 p.450
“Data hugging” blocks independent verification of medical AI. Apple claims age estimation with a mean absolute error of 2.9 years using photoplethysmographic (PPG) signals. Given PPG’s noise, such accuracy is questionable, raising concerns about other tech companies’ claims. Using UK Biobank data, w...
CardiologyComputational biology and bioinformaticsHealth careMedical research
10.1038/S44387-026-00094-2
ISSN:3005-1460
Large-scale whole-exome sequencing analyses identified protein-coding variants associated with immune-mediated diseases in 350,770 adults
Liu Yang•Ya-Nan Ou•Bang-Sheng Wu•Wei-Shi Liu•Yue-Ting Deng等 15 人
Nature Communications
2024
•2024/7/15
•Vol.15 No.1 p.1-15
The genetic contribution of protein-coding variants to immune-mediated diseases (IMDs) remains underexplored. Through whole exome sequencing of 40 IMDs in 350,770 UK Biobank participants, we identified 162 unique genes in 35 IMDs, among which 124 were novel genes. Several genes, including FLG which ...
Autoimmune diseasesGenetic association studyImmunology
10.1038/S41467-024-49782-0
ISSN:2041-1723
Cheese consumption and lower cholelithiasis risk a prospective UK biobank study with HDL-C mediation
Wenwen Yang•Zhixian Bao•Yuhua Chen•Jie Gao•Rui Ji
Npj Science Of Food
2026
•2026/1/30
•Vol.10 No.1 p.280
Cholelithiasis affects 10–20% of adults globally, and while cheese consumption may influence risk, underlying biological pathways remain unclear. In this prospective cohort study of 399,467 UK Biobank participants without prior cholelithiasis, we examined cheese intake frequency (never to ≥1/day) vi...
Biliary tract diseaseNutritionPredictive markersRisk factors
10.1038/S41538-025-00644-Z
ISSN:2396-8370
The risk of social isolation and loneliness on progression from incident cardiovascular disease to subsequent depression
Xin Qi•Shiqiang Cheng•Jin Yang•Li Liu•Jingcan Hao等 11 人
Nature Mental Health
2025
•2025/4/29
•00 p.1-9
Loneliness and social isolation are crucial triggers in the development of cardiovascular disease (CVD) and depression. This study aimed to explore the associations of loneliness and social isolation with the transition from incident CVD to subsequent depression. Multistate models were constructed t...
Psychology
10.1038/S44220-025-00418-2
ISSN:2731-6076
Distributed genetic architecture across the hippocampal formation implies common neuropathology across brain disorders
Bahrami Shahram•Nordengen Kaja•Shadrin Alexey A.•Frei Oleksandr•van der Meer Dennis等 9 人
Nature Communications
2022
•2022/6/15
•Vol.13 No.1 p.1-9
Despite its major role in complex human functions across the lifespan, most notably navigation, learning and memory, much of the genetic architecture of the hippocampal formation is currently unexplored. Here, through multivariate genome-wide association analysis in volumetric data from 35,411 white...
Genetics of the nervous systemGenome-wide association studiesNeurological disorders
10.1038/S41467-022-31086-W
ISSN:2041-1723
Changes in abdominal subcutaneous adipose tissue thickness associate with disease and anthropometric factors
Marjola Thanaj•Nicolas Basty•Madeleine Cule•Elena P. Sorokin•Brandon Whitcher等 8 人
International Journal Of Obesity
2025
•2025/7/9
•00 p.1-10
Three-dimensional (3D) mesh-derived phenotypes enable detailed characterisation of organ morphology and regional variation through statistical parametric maps (SPMs) and statistical shape analysis (SSA). While these techniques have been widely used for organ studies, their application to abdominal s...
Cardiovascular diseasesRisk factors
10.1038/S41366-025-01829-Y
ISSN:0307-0565
Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways
Philip R. Jansen•Kyoko Watanabe•Sven Stringer•Nathan Skene•Julien Bryois等 13 人
Nature Genetics
2019
•2019/2/25
•Vol.51 No.3 p.394-403
Insomnia is the second most prevalent mental disorder, with no sufficient treatment available. Despite substantial heritability, insight into the associated genes and neurobiological pathways remains limited. Here, we use a large genetic association sample (n = 1,331,010) to detect novel loci and ga...
Genetic association studyPsychiatric disorders
10.1038/S41588-018-0333-3
ISSN:1061-4036
Energy inefficiency underpinning brain state dysregulation in individuals with major depressive disorder
Qianhui Liu•Hui Xiong•Weiyang Shi•Shiqi Di•Xinle Cheng等 9 人
Nature Mental Health
2026
•2026/2/12
•Vol.4 No.3 p.400-415
Disruptions in brain state dynamics are a hallmark of major depressive disorder (MDD), yet their underlying mechanisms remain unclear. Here, building on network control theory, this case–control study reveals that energy inefficiency, characterized by elevated energy costs and reduced control stabil...
DepressionNeuroscience
10.1038/S44220-025-00583-4
ISSN:2731-6076
Healthy sleep patterns and risk of hospitalization for infection: a large community-based cohort study
Hong-Min Li•Xi-Ru Zhang•Dan-Qing Liao•Jian Gao•Cheng-Shen Qiu等 19 人
Translational Psychiatry
2025
•2025/3/27
•Vol.15 No.1 p.1-12
Sleep behaviours are potentially modifiable risk factors for infectious disease. However, little is known about the combined effects of multiple sleep factors on the risk of infections. We investigated the prospective associations of combined healthy sleep patterns with the risk of hospitalization f...
DiseasesHuman behaviourScientific community
10.1038/S41398-025-03314-6
ISSN:2158-3188
Proteogenomic links to human metabolic diseases
Koprulu Mine•Carrasco-Zanini Julia•Wheeler Eleanor•Lockhart Sam•Kerrison Nicola D.等 8 人
Nature Metabolism
2023
•2023/2/23
•00 p.1-13
Studying the plasma proteome as the intermediate layer between the genome and the phenome has the potential to identify new disease processes. Here, we conducted a cis-focused proteogenomic analysis of 2,923 plasma proteins measured in 1,180 individuals using antibody-based assays. We (1) identify 2...
Computational biology and bioinformaticsGeneticsMedical genomicsMetabolism
10.1038/S42255-023-00753-7
ISSN:2522-5812
Characterizing the phenotypic and genetic structure of psychopathology in UK Biobank
Camille M. Williams•Hugo Peyre•Tobias Wolfram•Younga H. Lee•Jakob Seidlitz等 9 人
Nature Mental Health
2024
•2024/7/4
•Vol.2 No.8 p.960-974
Mental health conditions are characterized by higher-order transdiagnostic factor structures, which may contribute to the high levels of comorbidity observed in psychopathology. However, the phenotypic and genetic structures of various psychopathology diagnoses may differ, raising questions about th...
Genetic variationPsychology
10.1038/S44220-024-00272-8
ISSN:2731-6076
UK Biobank data demonstrate long-term exposure to floods is a risk factor for incident dementia
Yao Wu•Rongbin Xu•Danijela Gasevic•Zhengyu Yang•Pei Yu等 13 人
Communications Medicine
2025
•2025/3/10
•Vol.5 No.1 p.1-9
Flooding has emerged as the most prevalent natural disaster, impacting billions of individuals worldwide. However, the long-term effects of flooding exposure on dementia remain unclear. With a nested case-control design, a risk-set sampling method was used to match cases and controls. Annual cumulat...
DementiaEpidemiology
10.1038/S43856-025-00771-4
ISSN:2730-664X
Prediction and stratification of longitudinal risk for chronic obstructive pulmonary disease across smoking behaviors
Yixuan He•David C. Qian•James A. Diao•Michael H. Cho•Edwin K. Silverman等 9 人
Nature Communications
2023
•2023/12/14
•Vol.14 No.1 p.1-9
Smoking is the leading risk factor for chronic obstructive pulmonary disease (COPD) worldwide, yet many people who never smoke develop COPD. We perform a longitudinal analysis of COPD in the UK Biobank to derive and validate the Socioeconomic and Environmental Risk Score which captures additive and ...
Genome-wide association studiesMedical geneticsPredictive medicine
10.1038/S41467-023-44047-8
ISSN:2041-1723
Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots
Albiñana Clara•Zhu Zhihong•Borbye-Lorenzen Nis•Boelt Sanne Grundvad•Cohen Arieh S.等 21 人
Nature Communications
2023
•2023/2/15
•Vol.14 No.1 p.1-16
The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping id...
EpidemiologyGenetics research
10.1038/S41467-023-36392-5
ISSN:2041-1723
The genetic architecture of sporadic and multiple consecutive miscarriage
Triin Laisk•Ana Luiza G. Soares•Teresa Ferreira•Jodie N. Painter•Jenny C. Censin等 55 人
Nature Communications
2020
•2020/11/25
•Vol.11 No.1 p.1-12
Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive m...
Genome-wide association studiesInfertility
10.1038/S41467-020-19742-5
ISSN:2041-1723
SMR-Portal: an online platform for integrative analysis of GWAS and xQTL data to identify complex trait genes
Yazhou Guo•Tao Xu•Jie Luo•Zhuqing Jiang•Wenhao Chen等 8 人
Nature Methods
2024
•2024/12/2
•00 p.1-3
Genetic databasesPopulation geneticsQuantitative traitSoftware
10.1038/S41592-024-02561-7
ISSN:1548-7091
Genetic control of DNA methylation is largely shared across European and East Asian populations
Alesha A. Hatton•Fei-Fei Cheng•Tian Lin•Ren-Juan Shen•Jie Chen等 19 人
Nature Communications
2024
•2024/3/28
•Vol.15 No.1 p.1-12
DNA methylation is an ideal trait to study the extent of the shared genetic control across ancestries, effectively providing hundreds of thousands of model molecular traits with large QTL effect sizes. We investigate cis DNAm QTLs in three European (n = 3701) and two East Asian (n = 2099) cohorts to...
DNA methylationEpigenomicsGenome-wide association studies
10.1038/S41467-024-47005-0
ISSN:2041-1723
Investigating the effects of genetic risk of schizophrenia on behavioural traits
Adam Socrates•Jessye Maxwell•Kylie P. Glanville•Marta Di Forti•Robin M. Murray等 7 人
Npj Schizophrenia
2021
•2021/1/22
•Vol.7 No.1 p.1-9
To characterise the trait-effects of increased genetic risk for schizophrenia, and highlight potential risk mediators, we test the association between schizophrenia polygenic risk scores (PRSs) and 529 behavioural traits (personality, psychological, lifestyle, nutritional) in the UK Biobank. Our pri...
BiomarkersSchizophrenia
10.1038/S41537-020-00131-2
ISSN:2334-265X
Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour
Melinda C. Mills•Felix C. Tropf•David M. Brazel•Natalie van Zuydam•Ahmad Vaez等 12 人
Nature Human Behaviour
2021
•2021/7/1
•00 p.1-14
Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with ...
Behavioural geneticsGenome-wide association studiesSociology
10.1038/S41562-021-01135-3
ISSN:2397-3374
An atlas of genetic effects on cellular composition of the tumor microenvironment
Yimin Cai•Zequn Lu•Can Chen•Ying Zhu•Zhirui Chen等 32 人
Nature Immunology
2024
•2024/9/2
•00 p.1-17
Deciphering the composition of the tumor microenvironment (TME) is critical for understanding tumorigenesis and to design immunotherapies. In the present study, we mapped genetic effects on cell-type proportions using single-cell and bulk RNA sequencing data, identifying 3,494 immunity quantitative ...
Cancer immunotherapyTumour immunology
10.1038/S41590-024-01945-3
ISSN:1529-2908
Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease
Scott E. Youlten•John P. Kemp•John G. Logan•Elena J. Ghirardello•Claudio M. Sergio等 37 人
Nature Communications
2021
•2021/5/5
•Vol.12 No.1 p.1-21
Osteocytes are master regulators of the skeleton. We mapped the transcriptome of osteocytes from different skeletal sites, across age and sexes in mice to reveal genes and molecular programs that control this complex cellular-network. We define an osteocyte transcriptome signature of 1239 genes that...
BioinformaticsGene expression analysisRNA sequencingSkeleton
10.1038/S41467-021-22517-1
ISSN:2041-1723
A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk
Marc Ferrell•Zeneng Wang•James T. Anderson•Xinmin S. Li•Marco Witkowski等 19 人
Nature Medicine
2024
•2024/2/19
•Vol.30 No.2 p.424-434
Despite intensive preventive cardiovascular disease (CVD) efforts, substantial residual CVD risk remains even for individuals receiving all guideline-recommended interventions. Niacin is an essential micronutrient fortified in food staples, but its role in CVD is not well understood. In this study, ...
Cardiovascular diseasesMetabolomicsRisk factors
10.1038/S41591-023-02793-8
ISSN:1078-8956
Plant-based diet quality, fat mass, and cardiovascular disease: A mediation analysis of mid-aged adults in the UK Biobank
Laura E. Marchese•Sarah A. McNaughton•Gilly A. Hendrie•Barbara Brayner•Kacie M. Dickinson等 6 人
European Journal Of Clinical Nutrition
2026
•2026/4/1
•00 p.1-8
Evidence supports plant-based diets for preventing cardiovascular diseases (CVD). Fat mass is a strong predictor of CVD, however it is unclear whether this mediates the relationship between plant-based diets and CVD. Thus, this study aimed to determine if longitudinal associations between plant-base...
Cardiovascular diseasesNutrition
10.1038/S41430-026-01731-4
ISSN:0954-3007
Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease
Alexander T. Williams•Jing Chen•Kayesha Coley•Chiara Batini•Abril Izquierdo等 32 人
Nature Communications
2023
•2023/10/23
•Vol.14 No.1 p.1-14
Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total samp...
Genetics researchGenome-wide association studiesThyroid diseases
10.1038/S41467-023-42284-5
ISSN:2041-1723
Associations of dietary patterns with brain health from behavioral, neuroimaging, biochemical and genetic analyses
Ruohan Zhang•Bei Zhang•Chun Shen•Barbara J. Sahakian•Zeyu Li等 10 人
Nature Mental Health
2024
•2024/4/1
•00 p.1-18
Food preferences significantly influence dietary choices, yet understanding natural dietary patterns in populations remains limited. Here we identifiy four dietary subtypes by applying data-driven approaches to food-liking data from 181,990 UK Biobank participants: ‘starch-free or reduced-starch’ (s...
Brain imagingData mining
10.1038/S44220-024-00226-0
ISSN:2731-6076
Combining SNP-to-gene linking strategies to identify disease genes and assess disease omnigenicity
Gazal Steven•Weissbrod Omer•Hormozdiari Farhad•Dey Kushal K.•Nasser Joseph等 13 人
Nature Genetics
2022
•2022/6/6
•Vol.54 No.6 p.827-836
Disease-associated single-nucleotide polymorphisms (SNPs) generally do not implicate target genes, as most disease SNPs are regulatory. Many SNP-to-gene (S2G) linking strategies have been developed to link regulatory SNPs to the genes that they regulate in cis. Here, we developed a heritability-base...
DiseasesGene regulationGenome-wide association studies
10.1038/S41588-022-01087-Y
ISSN:1061-4036
Integration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment
Junyi Xin•Dongying Gu•Shuwei Li•Sangni Qian•Yifei Cheng等 16 人
Nature Communications
2024
•2024/4/8
•Vol.15 No.1 p.1-11
The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a ge...
Cancer epidemiologyGenetic association studyPrognostic markers
10.1038/S41467-024-47204-9
ISSN:2041-1723
Heterogeneous effects of genetic variants and traits associated with fasting insulin on cardiometabolic outcomes
Magdalena Sevilla-González•Kirk Smith•Ningyuan Wang•Aubrey E. Jensen•Elizabeth M. Litkowski等 28 人
Nature Communications
2025
•2025/3/15
•Vol.16 No.1 p.1-12
Elevated fasting insulin levels (FI), indicative of altered insulin secretion and sensitivity, may precede type 2 diabetes (T2D) and cardiovascular disease onset. In this study, we group FI-associated genetic variants based on their genetic and phenotypic similarities and identify seven clusters wit...
EpidemiologyPre-diabetesRisk factors
10.1038/S41467-025-57452-Y
ISSN:2041-1723
Identifying individuals with high risk of Alzheimer’s disease using polygenic risk scores
Ganna Leonenko•Emily Baker•Joshua Stevenson-Hoare•Annerieke Sierksma•Mark Fiers等 8 人
Nature Communications
2021
•2021/7/23
•Vol.12 No.1 p.1-10
Polygenic Risk Scores (PRS) for AD offer unique possibilities for reliable identification of individuals at high and low risk of AD. However, there is little agreement in the field as to what approach should be used for genetic risk score calculations, how to model the effect of APOE, what the optim...
Alzheimer's diseaseGeneticsGenome-wide association studiesNeurology
10.1038/S41467-021-24082-Z
ISSN:2041-1723
Evaluating and improving heritability models using summary statistics
Doug Speed•John Holmes•David J. Balding
Nature Genetics
2020
•2020/3/23
•Vol.52 No.4 p.458-462
There is currently much debate regarding the best model for how heritability varies across the genome. The authors of GCTA recommend the GCTA-LDMS-I model, the authors of LD Score Regression recommend the Baseline LD model, and we have recommended the LDAK model. Here we provide a statistical framew...
Genetic association studyGenetics research
10.1038/S41588-020-0600-Y
ISSN:1061-4036
Early detection of Parkinson’s disease through multiplex blood and urine biomarkers prior to clinical diagnosis
Shuo Gao•Zheng Wang•Yuanfeng Huang•Guang yang•Yijing Wang等 14 人
Npj Parkinson's Disease
2025
•2025/2/25
•Vol.11 No.1 p.1-11
Blood and urine biomarkers are commonly used to diagnose and monitor chronic diseases. We initially screened 67 biomarkers, including 4 urine biomarkers and 63 blood biomarkers, and identified 13 blood biomarkers significantly associated with Parkinson’s disease (PD). Among these, we discovered thre...
Medical geneticsNeurodegenerationPredictive markers
10.1038/S41531-025-00888-2
ISSN:2373-8057
Efficient variance components analysis across millions of genomes
Ali Pazokitoroudi•Yue Wu•Kathryn S. Burch•Kangcheng Hou•Aaron Zhou等 7 人
Nature Communications
2020
•2020/8/11
•Vol.11 No.1 p.1-10
While variance components analysis has emerged as a powerful tool in complex trait genetics, existing methods for fitting variance components do not scale well to large-scale datasets of genetic variation. Here, we present a method for variance components analysis that is accurate and efficient: cap...
Heritable quantitative traitStatistical methods
10.1038/S41467-020-17576-9
ISSN:2041-1723
Genetic footprints of assortative mating in the Japanese population
Yamamoto Kenichi•Sonehara Kyuto•Namba Shinichi•Konuma Takahiro•Masuko Hironori等 11 人
Nature Human Behaviour
2022
•2022/9/22
•Vol.7 No.1 p.65-73
Assortative mating (AM) is a pattern characterized by phenotypic similarities between mating partners. Detecting the evidence of AM has been challenging due to the lack of large-scale datasets that include phenotypic data on both partners, especially in populations of non-European ancestries. Gameti...
Genetic variationGenome-wide association studiesSocial evolution
10.1038/S41562-022-01438-Z
ISSN:2397-3374
A Mendelian randomization analysis of cardiac MRI measurements as surrogate outcomes for heart failure and atrial fibrillation
A. F. Schmidt•C. Finan•J. van Setten•E. Puyol-Antón•B. Ruijsink等 10 人
Communications Medicine
2025
•2025/4/19
•Vol.5 No.1 p.1-7
Drug development and disease prevention of heart failure (HF) and atrial fibrillation (AF) are impeded by a lack of robust early-stage surrogates. We determined to what extent cardiac magnetic resonance (CMR) measurements act as surrogates for the development of HF or AF. Genetic data were sourced o...
ArrhythmiasCardiologyHeart failure
10.1038/S43856-025-00855-1
ISSN:2730-664X
Epidemiological associations between obesity, metabolism and disease risk: are body mass index and waist-hip ratio all you need?
Ville-Petteri Mäkinen•Siyu Zhao•Andrei Ihanus•Tuulia Tynkkynen•Mika Ala-Korpela
International Journal Of Obesity
2025
•2025/9/19
•00 p.1-6
Tracking excess adiposity at population scale is essential for managing the obesity pandemic in human populations. New formulas based on weight, height, waist and hip measurements have been suggested as better alternatives to the classic body mass index and waist-hip ratio, but the lack of systemati...
EpidemiologyObesity
10.1038/S41366-025-01895-2
ISSN:0307-0565
Functional disease architectures reveal unique biological role of transposable elements
Farhad Hormozdiari•Bryce van de Geijn•Joseph Nasser•Omer Weissbrod•Steven Gazal等 11 人
Nature Communications
2019
•2019/9/6
•Vol.10 No.1 p.1-8
Transposable elements (TE) comprise roughly half of the human genome. Though initially derided as junk DNA, they have been widely hypothesized to contribute to the evolution of gene regulation. However, the contribution of TE to the genetic architecture of diseases remains unknown. Here, we analyze ...
DNA transposable elementsGenetic markersGenetic predisposition to diseaseGenome-wide association studies
10.1038/S41467-019-11957-5
ISSN:2041-1723
Polygenic scoring accuracy varies across the genetic ancestry continuum
Yi Ding•Kangcheng Hou•Ziqi Xu•Aditya Pimplaskar•Ella Petter等 10 人
Nature
2023
•2023/5/17
•00 p.1-8
Polygenic scores (PGSs) have limited portability across different groupings of individuals (for example, by genetic ancestries and/or social determinants of health), preventing their equitable use1–3. PGS portability has typically been assessed using a single aggregate population-level statistic (fo...
GeneticsGenome-wide association studiesRisk factorsStatistical methods
10.1038/S41586-023-06079-4
ISSN:0028-0836
Artificial intelligence-enhanced electrocardiography derived body mass index as a predictor of future cardiometabolic disease
Libor Pastika•Arunashis Sau•Konstantinos Patlatzoglou•Ewa Sieliwonczyk•Antônio H. Ribeiro等 15 人
Npj Digital Medicine
2024
•2024/6/25
•Vol.7 No.1 p.1-16
The electrocardiogram (ECG) can capture obesity-related cardiac changes. Artificial intelligence-enhanced ECG (AI-ECG) can identify subclinical disease. We trained an AI-ECG model to predict body mass index (BMI) from the ECG alone. Developed from 512,950 12-lead ECGs from the Beth Israel Deaconess ...
DyslipidaemiasMachine learningObesityPrognostic markers
10.1038/S41746-024-01170-0
ISSN:2398-6352
Genetic predisposition to mosaic Y chromosome loss in blood
Deborah J. Thompson•Giulio Genovese•Jonatan Halvardson•Jacob C. Ulirsch•Daniel J. Wright等 39 人
Nature
2019
•2019/11/20
•Vol.575 No.7784 p.652-657
Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1–5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational approach, we estimate that 20% of the male population represented in the UK Biobank stud...
Cancer genomicsCell divisionGenome-wide association studiesGenomic instabilityHaematopoietic system
10.1038/S41586-019-1765-3
ISSN:0028-0836
Association of life course adiposity with risk of incident dementia: a prospective cohort study of 322,336 participants
Deng Yue-Ting•Li Yu-Zhu•Huang Shu-Yi•Ou Ya-Nan•Zhang Wei等 14 人
Molecular Psychiatry
2022
•2022/5/10
•00 p.1-11
Cohort studies report inconsistent associations between body mass index (BMI) and all-cause incident dementia. Furthermore, evidence on fat distribution and body composition measures are scarce and few studies estimated the association between early life adiposity and dementia risk. Here, we include...
Molecular biologyNeuroscience
10.1038/S41380-022-01604-9
ISSN:1359-4184
Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent
Christopher Hübel•Héléna A. Gaspar•Jonathan R. I. Coleman•Ken B. Hanscombe•Kirstin Purves等 12 人
Nature Communications
2019
•2019/12/18
•Vol.10 No.1 p.1-12
Body composition is often altered in psychiatric disorders. Using genome-wide common genetic variation data, we calculate sex-specific genetic correlations amongst body fat %, fat mass, fat-free mass, physical activity, glycemic traits and 17 psychiatric traits (up to N = 217,568). Two patterns emer...
Endocrine system and metabolic diseasesFat metabolismGenetic association studyPsychiatric disorders
10.1038/S41467-019-13544-0
ISSN:2041-1723
Polygenic prediction of body mass index and obesity through the life course and across ancestries
Roelof A. J. Smit•Kaitlin H. Wade•Qin Hui•Joshua D. Arias•Xianyong Yin等 627 人
Nature Medicine
2025
•2025/7/21
•00 p.1-18
Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the ...
ObesityPredictive markers
10.1038/S41591-025-03827-Z
ISSN:1078-8956
Association of time spent in outdoor light and genetic risk with the incidence of depression
Lin Jing•Yang Hongxi•Zhang Yuan•Cao Zhi•Li Dun等 8 人
Translational Psychiatry
2023
•2023/2/3
•Vol.13 No.1 p.1-9
Depression is the consequence of both environment and genes working together. Genetic factors increase depression risk, but it is unclear whether this association can be offset by time spent in outdoor light. The study was undertaken to investigate the optimal time spent in outdoor light for lowerin...
DepressionGeneticsHuman behaviour
10.1038/S41398-023-02338-0
ISSN:2158-3188
Exome sequencing identifies novel genes associated with cerebellar volume and microstructure
Yuanyuan Liang•Dongrui Ma•Mengjie Li•Zhiyun Wang•Chenwei Hao等 16 人
Communications Biology
2025
•2025/3/1
•Vol.8 No.1 p.1-11
Proteins encoded by exons are critical for cellular functions, and mutations in these genes often result in significant phenotypic effects. The cerebellum is linked to various heritable human disease phenotypes, yet genome-wide association studies have struggled to capture the effects of rare varian...
GenomicsNeurological disorders
10.1038/S42003-025-07797-3
ISSN:2399-3642
Photoreceptor layer thinning is an early biomarker for type 2 diabetes: a cohort study in UK Biobank
Yiyuan Ma•Yue Wu•Leyi Hu•Xinyu Zhang•Danying Zheng等 7 人
Eye
2025
•2025/10/3
•00 p.1-7
To investigate the association between photoreceptor outer segment (POS) thickness and the risk of T2D. This prospective cohort study included 35,024 UK Biobank participants with high-quality optical coherence tomography (OCT) images, excluding individuals with neurological or ocular diseases. Cox p...
Metabolic disordersPredictive markers
10.1038/S41433-025-04068-7
ISSN:0950-222X
Associations between shorter leucocyte telomere length and increased risk of age-related macular degeneration in women: insights from the United Kingdom Biobank study
Can Can Xue•Simon Nusinovici•Marco Yu•Miao-Li Chee•Kelvin Teo等 10 人
Eye
2024
•2024/12/24
•00 p.1-7
To determine the association between telomere length (TL) and age-related macular degeneration (AMD) and examine the potential variations with sex and ethnicity. Population-based, cross-sectional study. A total of 52,083 participants from the UK Biobank were included. Leucocyte TL, measured using qu...
Macular degenerationRisk factors
10.1038/S41433-024-03566-4
ISSN:0950-222X
Association between metabolic signatures of predicted VAT mass and risk of MASLD and other chronic liver diseases
Shi-Ao Wang•Hao-Wen Chen•Qi Zhong•Zheng-Yun Xu•Yan-Fei Wei等 11 人
International Journal Of Obesity
2026
•2026/4/1
•00 p.1-11
Visceral adipose tissue (VAT) plays a key role in metabolic dysfunction, and it is increasingly recognised as a contributor to metabolic dysfunction-associated steatotic liver disease (MASLD) and other chronic liver conditions. However, the systemic metabolic pathways linking VAT to liver disease re...
Digestive signs and symptomsEpidemiologyObesity
10.1038/S41366-026-02067-6
ISSN:0307-0565