Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
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Xiangrui Meng; Georgina Navoly; Olga Giannakopoulou; Daniel F. Levey; Dora Koller; Gita A. Pathak; Koen, Nastassja; +76 Authors
Xiangrui Meng; Georgina Navoly; Olga Giannakopoulou; Daniel F. Levey; Dora Koller; Gita A. Pathak; Koen, Nastassja; Lin, Kuang; Adams, Mark J.; Rentería, Miguel E.; Feng, Yanzhe; Gaziano, J. Michael; Stein, Dan J.; Zar, Heather J.; Campbell, Megan L.; van Heel, David A.; Trivedi, Bhavi; Finer, Sarah; McQuillin, Andrew; Bass, Nick; Chundru, V. Kartik; Martin, Hilary C.; Huang, Qin Qin; Valkovskaya, Maria; Chu, Chia-Yi; Kanjira, Susan; Kuo, Po-Hsiu; Chen, Hsi-Chung; Tsai, Shih-Jen; Liu, Yu-Li; Kendler, Kenneth S.; Peterson, Roseann E.; Cai, Na; Fang, Yu; Sen, Srijan; Scott, Laura J.; Burmeister, Margit; Loos, Ruth J. F.; Preuss, Michael H.; Actkins, Ky'Era V.; Davis, Lea K.; Uddin, Monica; Wani, Agaz H; Wildman, Derek E.; Aiello, Allison E.; Ursano, Robert J.; Kessler, Ronald C.; Kanai, Masahiro; Okada, Yukinori; Sakaue, Saori; Rabinowitz, Jill; Maher, Brion S.; Uhl, George; Eaton, William; Cruz-Fuentes, Carlos S.; Martinez-Levy, Gabriela A.; Campos, Adrian I.; Millwood, Iona Y.; Chen, Zhengming; Li, Liming; Wassertheil-Smoller, Sylvia; Jiang, Yunxuan; Tian, Chao; Martin, Nicholas G.; Mitchell, Brittany L.; Byrne, Enda M.; Awasthi, Swapnil; Coleman, Jonathan R. I.; Ripke, Stephan; PGC MDD Working Group; China Kadoorie Biobank Collaborative Group; the 23andMe Research Team; Genes & Health Research Team; BioBank Japan Project; Sofer, Tamar; Walters, Robin G.; McIntosh, Andrew M.; Polimanti, Renato; Dunn, Erin C.; Stein, Murray B.; Gelernter, Joel; Lewis, Cathryn M.; Kuchenbaecker, Karoline;
Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
AbstractMost 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.
Germany, United Kingdom, Denmark, United States
- Broad Institute United States
- Harvard University United States
- University of Michigan–Flint United States
- University of California, San Diego United States
- Novo Nordisk Foundation Center for Basic Metabolic Research Denmark
Depressive Disorder, Major Depressive Disorder, Depression, 610, Major, Chromosome Mapping, Single Nucleotide, Genome-wide association studies, Polymorphism, Single Nucleotide, Article, multi ancestry, Humans, GWAS, Genetic Predisposition to Disease, Polymorphism, major depression, Genome-Wide Association Study
Depressive Disorder, Major Depressive Disorder, Depression, 610, Major, Chromosome Mapping, Single Nucleotide, Genome-wide association studies, Polymorphism, Single Nucleotide, Article, multi ancestry, Humans, GWAS, Genetic Predisposition to Disease, Polymorphism, major depression, Genome-Wide Association Study
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EC| ATTENTIVE, WT| Understanding the genetic basis of common human diseases: core funding for the Wellcome Trust Centre for Human Genetics., NIH| Childhood adversity, DNA methylation, and risk for depression: A longitudinal study of sensitive periods in development, NIH| Investigating the Systems Genetics of the Patterns of Polysubstance Abuse and Addiction
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