Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
-
Published:2024-01-04
Issue:
Volume:
Page:
-
ISSN:1061-4036
-
Container-title:Nature Genetics
-
language:en
-
Short-container-title:Nat Genet
Author:
Meng XiangruiORCID, Navoly Georgina, Giannakopoulou Olga, Levey Daniel F.ORCID, Koller DoraORCID, Pathak Gita A., Koen Nastassja, Lin Kuang, Adams Mark J.ORCID, Rentería Miguel E.ORCID, Feng Yanzhe, Gaziano J. Michael, Stein Dan J.ORCID, Zar Heather J., Campbell Megan L.ORCID, van Heel David A.ORCID, Trivedi Bhavi, Finer SarahORCID, McQuillin AndrewORCID, Bass Nick, Chundru V. KartikORCID, Martin Hilary C., Huang Qin QinORCID, Valkovskaya Maria, Chu Chia-YiORCID, Kanjira Susan, Kuo Po-HsiuORCID, Chen Hsi-ChungORCID, Tsai Shih-JenORCID, Liu Yu-Li, Kendler Kenneth S.ORCID, Peterson Roseann E.ORCID, Cai NaORCID, Fang YuORCID, Sen Srijan, Scott Laura J.ORCID, Burmeister MargitORCID, Loos Ruth J. F.ORCID, Preuss Michael H.ORCID, Actkins Ky’Era V., Davis Lea K.ORCID, Uddin Monica, Wani Agaz H., Wildman Derek E.ORCID, Aiello Allison E., Ursano Robert J.ORCID, Kessler Ronald C.ORCID, Kanai MasahiroORCID, Okada YukinoriORCID, Sakaue SaoriORCID, Rabinowitz Jill A., Maher Brion S.ORCID, Uhl George, Eaton William, Cruz-Fuentes Carlos S.ORCID, Martinez-Levy Gabriela A.ORCID, Campos Adrian I.ORCID, Millwood Iona Y.ORCID, Chen Zhengming, Li LimingORCID, Wassertheil-Smoller SylviaORCID, Jiang Yunxuan, Tian Chao, Martin Nicholas G.ORCID, Mitchell Brittany L.ORCID, Byrne Enda M.ORCID, Awasthi Swapnil, Coleman Jonathan R. I.ORCID, Ripke StephanORCID, Sofer TamarORCID, Walters Robin G.ORCID, McIntosh Andrew M.ORCID, Polimanti RenatoORCID, Dunn Erin C., Stein Murray B.ORCID, Gelernter JoelORCID, Lewis Cathryn M.ORCID, Kuchenbaecker KarolineORCID, , , , ,
Abstract
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.
Publisher
Springer Science and Business Media LLC
Reference98 articles.
1. 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). 2. Wray, N. R. et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat. Genet. 50, 668–681 (2018). 3. CONVERGE Consortium. Sparse whole-genome sequencing identifies two loci for major depressive disorder. Nature 523, 588–591 (2015). 4. Zhang, Y., Qi, G., Park, J.-H. & Chatterjee, N. Estimation of complex effect-size distributions using summary-level statistics from genome-wide association studies across 32 complex traits. Nat. Genet. 50, 1318–1326 (2018). 5. Flint, J. & Kendler, K. S. The genetics of major depression. Neuron 81, 1214 (2014).
|
|