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Meng, X.* ; Navoly, G.* ; Giannakopoulou, O.* ; Levey, D.F.* ; Koller, D.* ; Pathak, G.A.* ; Koen, N.* ; Lin, K.* ; Adams, M.J.* ; Rentería, M.E.* ; Feng, Y.* ; Gaziano, J.M.* ; Stein, D.J.* ; Zar, H.J.* ; Campbell, M.L.* ; van Heel, D.A.* ; Trivedi, B.* ; Finer, S.* ; McQuillin, A.* ; Bass, N.J.* ; Chundru, V.K.* ; Martin, H.C.* ; Huang, Q.Q.* ; Valkovskaya, M.* ; Chu, C.Y.* ; Kanjira, S.* ; Kuo, P.H.* ; Chen, H.C.* ; Tsai, S.J.* ; Liu, Y.L.* ; Kendler, K.S.* ; Peterson, R.E.* ; Cai, N. ; Fang, Y.J.* ; Sen, S.* ; Scott, L.J.* ; Burmeister, M.* ; Loos, R.J.F.* ; Preuss, M.H.* ; Actkins, K.V.* ; Davis, L.K.* ; Uddin, M.N.* ; Wani, A.H.* ; Wildman, D.E.* ; Aiello, A.E.* ; Ursano, R.J.* ; Kessler, R.C.* ; Kanai, M.* ; Okada, Y.* ; Sakaue, S.* ; Rabinowitz, J.A.* ; Maher, B.S.* ; Uhl, G.* ; Eaton, W.* ; Cruz-Fuentes, C.S.* ; Martinez-Levy, G.A.* ; Campos, A.I.* ; Millwood, I.Y.* ; Chen, Z.* ; Li, L.* ; Wassertheil-Smoller, S.* ; Jiang, Y.* ; Tian, C.* ; Martin, N.G.* ; Mitchell, B.L.* ; Byrne, E.M.* ; Awasthi, S.* ; Coleman, J.R.I.* ; Ripke, S.* ; Sofer, T.* ; Walters, R.G.* ; McIntosh, A.M.* ; Polimanti, R.* ; Dunn, E.C.* ; Stein, M.B.* ; Gelernter, J.* ; Lewis, C.M.* ; Kuchenbaecker, K.*

Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.

Nat. Genet. 56, 222-233 (2024)

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	Open Access Gold (Paid Option)

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Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Environment Interaction; Metaanalysis; Architecture; Expression; Regression; Symptoms; Gwas

ISSN (print) / ISBN 1061-4036

e-ISSN 1546-1718

Journal Nature Genetics

Quellenangaben Volume: 56, Issue: 2, Pages: 222-233

Publisher Nature Publishing Group

Publishing Place New York, NY

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Pioneer Campus (HPC)
Institute of Computational Biology (ICB)

Grants NHMRC
Yale Biological Sciences Training Program
One Mind Rising Star Award
NIH
European Commission
MSCA Individual Fellowship
Biotechnology and Biological Sciences Research Council
Wellcome
European Research Council under the European Union
Public Health England
Bradford Teaching Hospitals NHS Foundation Trust
Ministry of Science and Technology Project
National Health Research Institutes Project
National Taiwan University Career Development Project
National Health and Medical Research Council (NHMRC) of Australia
European Union
United States NIH
UK Research and Innovation
Wellcome Trust
East London NHS Foundation Trust
Newham, Redbridge
NHS Clinical Commissioning Groups (City and Hackney, Waltham Forest)
Clinical and Translational Science Awards
National Institutes of Health (NIH)
Vanderbilt University Medical Center's BioVU
NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation
VA Cooperative Studies Program
Veterans Affairs Office of Research and Development MVP grant
Yale Department of Psychiatry, Division of Human Genetics
Barts Health NHS Trust
Wellcome Sanger Institute
Social Genetic and Developmental Psychiatry Centre (King's College London)
NIHR National Biosample Centre (UK Biocentre)
CONVERGE consortium (China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology)
National Institute of Mental Health
VU University Amsterdam
Cancer Research UK
UK Medical Research Council
GlaxoSmithKline
National Natural Science Foundation of China
National Key Research and Development Program of China
British Heart Foundation
Dutch Brain Foundation
National Institute of Mental Health of the National Institutes of Health
Takeda Development Centre Americas Inc. - NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London
Merck Sharp Dohme LLC
GlaxoSmithKline Research and Development Limited
NHS National Institute for Health Research Clinical Research Network (North Thames) - Alnylam Pharmaceuticals, Genomics PLC
Barts Charity
Higher Education Funding Council for England Catalyst
Medical Research Council (UK)
Kadoorie Charitable Foundation in Hong Kong
NIA, VA, University of Maryland, Maryland VA Healthcare System, Baltimore Research and Education Foundation
Brain & Behavior Research Foundation NARSAD
NIMH
National Institute of Drug Abuse
NIMH - NHMRC
US Department of Defense
Cohen Veteran Bioscience, Mexico's National Institute of Psychiatry, Mexico's National Council of Science and Technology
National Heart, Lung, and Blood Institute (NHLBI)
NIDA
National Institutes of Health Award
Hispanic Community Health Study/Study of Latinos also received
NIDCR
NHLBI
NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases
San Diego State University
Albert Einstein College of Medicine