Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
38177345
TITLE
Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.
ABSTRACT
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.
© 2024. The Author(s).
DATE PUBLISHED
2024 Jan 04
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2022/07/21
accepted 2023/10/26
medline 2024/01/05 00:42
pubmed 2024/01/05 00:42
entrez 2024/01/04 23:24
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Meng X Meng Xiangrui X Division of Psychiatry, UCL, London, UK.
Navoly G Navoly Georgina G UCL Genetics Institute, UCL, London, UK.
Giannakopoulou O Giannakopoulou Olga O Division of Psychiatry, UCL, London, UK.
Levey DF Levey Daniel F DF Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Koller D Koller Dora D Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain.
Pathak GA Pathak Gita A GA Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Koen N Koen Nastassja N SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Lin K Lin Kuang K Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Adams MJ Adams Mark J MJ Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Rentería ME Rentería Miguel E ME Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Feng Y Feng Yanzhe Y Division of Psychiatry, UCL, London, UK.
Gaziano JM Gaziano J Michael JM Department of Medicine, Harvard Medical School, Boston, MA, USA.
Stein DJ Stein Dan J DJ SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Zar HJ Zar Heather J HJ SAMRC Unit on Child and Adolescent Health, Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Campbell ML Campbell Megan L ML Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
van Heel DA van Heel David A DA Blizard Institute, Queen Mary University of London, London, UK.
Trivedi B Trivedi Bhavi B Blizard Institute, Queen Mary University of London, London, UK.
Finer S Finer Sarah S Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
McQuillin A McQuillin Andrew A Division of Psychiatry, UCL, London, UK.
Bass N Bass Nick N Division of Psychiatry, UCL, London, UK.
Chundru VK Chundru V Kartik VK Wellcome Sanger Institute, Saffron Walden, UK.
Martin HC Martin Hilary C HC Wellcome Sanger Institute, Saffron Walden, UK.
Huang QQ Huang Qin Qin QQ Wellcome Sanger Institute, Saffron Walden, UK.
Valkovskaya M Valkovskaya Maria M Division of Psychiatry, UCL, London, UK.
Chu CY Chu Chia-Yi CY Division of Psychiatry, UCL, London, UK.
Kanjira S Kanjira Susan S Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Kuo PH Kuo Po-Hsiu PH Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
Chen HC Chen Hsi-Chung HC Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan.
Tsai SJ Tsai Shih-Jen SJ Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
Liu YL Liu Yu-Li YL Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan.
Kendler KS Kendler Kenneth S KS Department of Psychiatry, VCU, Richmond, VA, USA.
Peterson RE Peterson Roseann E RE Department of Psychiatry, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.
Cai N Cai Na N Department of Medicine, Technical University of Munich, Munich, Germany.
Fang Y Fang Yu Y Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
Sen S Sen Srijan S Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
Scott LJ Scott Laura J LJ Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Burmeister M Burmeister Margit M Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
Loos RJF Loos Ruth J F RJF Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Preuss MH Preuss Michael H MH Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Actkins KV Actkins Ky'Era V KV Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Davis LK Davis Lea K LK Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
Uddin M Uddin Monica M College of Public Health, University of South Florida, Tampa, FL, USA.
Wani AH Wani Agaz H AH College of Public Health, University of South Florida, Tampa, FL, USA.
Wildman DE Wildman Derek E DE Genomics Program, College of Public Health, University of South Florida, Tampa, FL, USA.
Aiello AE Aiello Allison E AE Robert N. Butler Columbia Aging Center, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Ursano RJ Ursano Robert J RJ Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Kessler RC Kessler Ronald C RC Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.
Kanai M Kanai Masahiro M Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Okada Y Okada Yukinori Y Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Sakaue S Sakaue Saori S Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Rabinowitz JA Rabinowitz Jill A JA Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Maher BS Maher Brion S BS Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Uhl G Uhl George G Neurology and Pharmacology, University of Maryland, Maryland VA Healthcare System, Baltimore, MD, USA.
Eaton W Eaton William W Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Cruz-Fuentes CS Cruz-Fuentes Carlos S CS Departamento de Genética, Instituto Nacional de Psiquiatría 'Ramón de la Fuente Muñíz', Mexico City, Mexico.
Martinez-Levy GA Martinez-Levy Gabriela A GA Departamento de Genética, Instituto Nacional de Psiquiatría 'Ramón de la Fuente Muñíz', Mexico City, Mexico.
Campos AI Campos Adrian I AI Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Millwood IY Millwood Iona Y IY MRC Population Health Research Unit, University of Oxford, Oxford, UK.
Chen Z Chen Zhengming Z MRC Population Health Research Unit, University of Oxford, Oxford, UK.
Li L Li Liming L Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China.
Wassertheil-Smoller S Wassertheil-Smoller Sylvia S Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Jiang Y Jiang Yunxuan Y 23andMe, Inc., Mountain View, CA, USA.
Tian C Tian Chao C 23andMe, Inc., Mountain View, CA, USA.
Martin NG Martin Nicholas G NG Mental Health and Neuroscience Research Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Mitchell BL Mitchell Brittany L BL Mental Health and Neuroscience Research Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Byrne EM Byrne Enda M EM Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia.
Awasthi S Awasthi Swapnil S Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
Coleman JRI Coleman Jonathan R I JRI Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Ripke S Ripke Stephan S Analytic and Translational Genetics Unit, Massachusetts General Hospital, Cambridge, MA, USA.
PGC-MDD Working Group
China Kadoorie Biobank Collaborative Group
23andMe Research Team
Genes and Health Research Team
BioBank Japan Project
Sofer T Sofer Tamar T Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Walters RG Walters Robin G RG MRC Population Health Research Unit, University of Oxford, Oxford, UK.
McIntosh AM McIntosh Andrew M AM Institute for Genomics and Cancer, University of Edinburgh, Edinburgh, UK.
Polimanti R Polimanti Renato R VA Connecticut Healthcare Center, West Haven, CT, USA.
Dunn EC Dunn Erin C EC Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
Stein MB Stein Murray B MB Psychiatry Service, VA San Diego Healthcare System, San Diego, CA, USA.
Gelernter J Gelernter Joel J Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Lewis CM Lewis Cathryn M CM Department of Medical and Molecular Genetics, King's College London, London, UK.
Kuchenbaecker K Kuchenbaecker Karoline K UCL Genetics Institute, UCL, London, UK. k.kuchenbaecker@ucl.ac.uk.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Nature genetics
ISOABBREVIATION: Nat Genet
YEAR: 2024
MONTH: Jan
DAY: 04
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
948561 EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
212360/ Z/18/Z Wellcome Trust (Wellcome)
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