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

Journal: Nature genetics

Volume: 56

Issue: 2

Year of Publication: 2024

Affiliated Institutions:  Division of Psychiatry, UCL, London, UK. UCL Genetics Institute, UCL, London, UK. Department of Psychiatry, VA CT Healthcare Center, West Haven, CT, USA. SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Nuffield Department of Population Health, University of Oxford, Oxford, UK. Division of Psychiatry, University of Edinburgh, Edinburgh, UK. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Department of Medicine, VA Boston Healthcare System, Boston, MA, USA. SAMRC Unit on Child and Adolescent Health, Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa. Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Blizard Institute, Queen Mary University of London, London, UK. Wolfson Institute of Population Health, Queen Mary University of London, London, UK. Wellcome Sanger Institute, Saffron Walden, UK. Department of Public Health and Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan. Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan. Institute of Brain Science and Division of Psychiatry, National Yang-Ming Chiao Tung University, Taipei, Taiwan. Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan. Department of Psychiatry, VCU, Richmond, VA, USA. Helmholtz Pioneer Campus, Helmholtz Munich, Neuherberg, Germany. Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA. Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. College of Public Health, University of South Florida, Tampa, FL, USA. Genomics Program, College of Public Health, University of South Florida, Tampa, FL, USA. Robert N. Butler Columbia Aging Center, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Department of Health Care Policy, Harvard Medical School, Boston, MA, USA. Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan. Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Neurology and Pharmacology, University of Maryland, Maryland VA Healthcare System, Baltimore, MD, USA. Departamento de Genética, Instituto Nacional de Psiquiatría 'Ramón de la Fuente Muñíz', Mexico City, Mexico. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA. Department of Biostatistics, Emory University, Atlanta, GA, USA. andMe, Inc., Mountain View, CA, USA. Mental Health and Neuroscience Research Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia. Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. Department of Psychiatry, UC San Diego School of Medicine, La Jolla, CA, USA. Division of Psychiatry, UCL, London, UK. k.kuchenbaecker@ucl.ac.uk.

Abstract summary 

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.

Authors & Co-authors:  Meng Xiangrui X Navoly Georgina G Giannakopoulou Olga O Levey Daniel F DF Koller Dora D Pathak Gita A GA Koen Nastassja N Lin Kuang K Adams Mark J MJ Rentería Miguel E ME Feng Yanzhe Y Gaziano J Michael JM Stein Dan J DJ Zar Heather J HJ Campbell Megan L ML van Heel David A DA Trivedi Bhavi B Finer Sarah S McQuillin Andrew A Bass Nick N Chundru V Kartik VK Martin Hilary C HC Huang Qin Qin QQ Valkovskaya Maria M Chu Chia-Yi CY Kanjira Susan S Kuo Po-Hsiu PH Chen Hsi-Chung HC Tsai Shih-Jen SJ Liu Yu-Li YL Kendler Kenneth S KS Peterson Roseann E RE Cai Na N Fang Yu Y Sen Srijan S Scott Laura J LJ Burmeister Margit M Loos Ruth J F RJF Preuss Michael H MH Actkins Ky'Era V KV Davis Lea K LK Uddin Monica M Wani Agaz H AH Wildman Derek E DE Aiello Allison E AE Ursano Robert J RJ Kessler Ronald C RC Kanai Masahiro M Okada Yukinori Y Sakaue Saori S Rabinowitz Jill A JA Maher Brion S BS Uhl George G Eaton William W Cruz-Fuentes Carlos S CS Martinez-Levy Gabriela A GA Campos Adrian I AI Millwood Iona Y IY Chen Zhengming Z Li Liming L Wassertheil-Smoller Sylvia S Jiang Yunxuan Y Tian Chao C Martin Nicholas G NG Mitchell Brittany L BL Byrne Enda M EM Awasthi Swapnil S Coleman Jonathan R I JRI Ripke Stephan S Sofer Tamar T Walters Robin G RG McIntosh Andrew M AM Polimanti Renato R Dunn Erin C EC Stein Murray B MB Gelernter Joel J Lewis Cathryn M CM Kuchenbaecker Karoline K

Study Outcome 

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Statistics
Citations :  GBD 2017 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1859–1922 (2018).
Authors :  83
Identifiers
Doi : 10.1038/s41588-023-01596-4
SSN : 1546-1718
Study Population
Male,Female
Mesh Terms
Humans
Other Terms
Study Design
Cross Sectional Study
Study Approach
Country of Study
Publication Country
United States