Multi-ancestry GWAS of major depression aids locus discovery, fine-mapping, gene prioritisation, and causal inference
Year: 2022
Type: preprint
Study design: Observational Study
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 studies with 88,316 MD cases and 902,757 controls to previously reported data from individuals of European ancestry. This includes samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latinx participants (32%). The multi-ancestry GWAS identified 190 significantly associated loci, 53 of them novel. For previously reported loci from GWAS in European ancestry the power-adjusted transferability ratio was 0.6 in the Hispanic/Latinx group and 0.3 in each of the other groups. Fine-mapping benefited from additional sample diversity: the number of credible sets with ≤5 variants increased from 3 to 12. A transcriptome-wide association study identified 354 significantly associated genes, 205 of them novel. Mendelian Randomisation showed a bidirectional relationship with BMI exclusively in samples of European ancestry. This first multi-ancestry GWAS of MD demonstrates the importance of large diverse samples for the identification of target genes and putative mechanisms.
Authors: Xiangrui Meng, Georgina Navoly, Olga Giannakopoulou, Daniel Levey, Dora Koller, Gita Pathak, Nastassja Koen, Kuang Lin, Miguel E. Rentería, Yanzhe Feng, J. Michael Gaziano, Dan J. Stein, Heather J. Zar, Megan L. Campbell, David A. van Heel, Bhavi Trivedi, Sarah Finer, Andrew McQuillin, Nick Bass, V. Kartik Chundru, Hilary Martin, Qin Qin Huang, Maria Valkovskaya, Po-Hsiu Kuo, Hsi-Chung Chen, Shih-Jen Tsai, Yu-Li Liu, Kenneth S. Kendler, Roseann E. Peterson, Na Cai, Yu Fang, Srijan Sen, Laura Scott, Margit Burmeister, Ruth Loos, Michael Preuss, Ky’Era V. Actkins, Lea K. Davis, Monica Uddin, Agaz Wani, Derek Wildman, Robert J. Ursano, Ronald C. Kessler, Masahiro Kanai, Yukinori Okada, Saori Sakaue, Jill Rabinowitz, Brion Maher, George Uhl, William Eaton, Carlos S. Cruz-Fuentes, Gabriela A. Martinez-Levy, Adrian I. Campos, Iona Y. Millwood, Zhengming Chen, Liming Li, Sylvia Wassertheil-Smoller, Yunxuan Jiang, Chao Tian, Nicholas G. Martin, Brittany L. Mitchell, Enda M. Byrne, Naomi R. Wray, Swapnil Awasthi, Jonathan R. I. Coleman, Stephan Ripke, PGC MDD Working Group, China Kadoorie Biobank Collaborative Group, Tamar Sofer, Robin G. Walters, Renato Polimanti, Erin C. Dunn, Murray B. Stein, Joel Gelernter, Cathryn Lewis, Karoline Kuchenbaecker
Institutions: University College London, Yale University, VA Connecticut Healthcare System, Universitat de Barcelona, South African Medical Research Council, University of Cape Town, University of Oxford, QIMR Berghofer Medical Research Institute, Brigham and Women's Hospital, Harvard University, VA Boston Healthcare System, Queen Mary University of London, Blizard Institute, Wellcome Sanger Institute, National Taiwan University, National Taiwan University Hospital, National Yang Ming Chiao Tung University, Taipei Veterans General Hospital, National Health Research Institutes, Virginia Commonwealth University, Virginia Commonwealth University Medical Center, SUNY Downstate Health Sciences University, Helmholtz Munich, University of Michigan, University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, Icahn School of Medicine at Mount Sinai, Vanderbilt University Medical Center, Vanderbilt University, University of South Florida, Uniformed Services University of the Health Sciences, Broad Institute, Massachusetts General Hospital, The University of Osaka, RIKEN Center for Integrative Medical Sciences, The University of Tokyo, Johns Hopkins University, VA Maryland Health Care System, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, The University of Queensland, Institute for Molecular Bioscience, MRC Population Health Research Unit, Peking University, Albert Einstein College of Medicine, Emory University, 23andMe (United States), University of California, Davis, Stanley Center for Psychiatric Research, King's College London, Stiftung Charité, Charité - Universitätsmedizin Berlin
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Defense, Office of Dietary Supplements, U.S. Department of Veterans Affairs, Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Yale University, Office of Research and Development, Alnylam Pharmaceuticals, Vanderbilt University, University of Miami, Northwestern University, San Diego State University, University of Washington, Virginia Commonwealth University, National Alliance for Research on Schizophrenia and Depression, Wellcome Trust, Vanderbilt University Medical Center, Broad Institute, UK Research and Innovation, Barts Charity, Georgia Clinical and Translational Science Alliance, One Mind, Maze Therapeutics, Cancer Research UK, National Institute for Health and Care Research, British Heart Foundation, King's College London, University College London, University of Oxford, European Commission, National Natural Science Foundation of China, Vrije Universiteit Amsterdam, Public Health England, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Novo Nordisk, National Health Research Institutes, National Taiwan University, Kadoorie Charitable Foundation, Barts Health NHS Trust, National Institutes of Health, Directorate for Biological Sciences, University of Illinois at Urbana-Champaign, NIHR Maudsley Biomedical Research Centre, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Health and Medical Research Council, National Key Research and Development Program of China, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, National Institute on Minority Health and Health Disparities, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Health Data Research UK
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OpenAlex ID: W4286492015