open access publication

Article, Early Access, 2024

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

NATURE GENETICS, ISSN 1061-4036, 1061-4036, 10.1038/s41588-023-01596-4

Contributors

Meng, Xiangrui 0000-0003-2360-423X [1] [2] Navoly, Georgina [1] [2] Giannakopoulou, Olga 0000-0001-8611-2094 [1] [2] Levey, Daniel F. [3] [4] Koller, Dora 0000-0002-0415-0466 [3] [4] [5] Pathak, Gita A. [3] [4] Koen, Nastassja [6] Lin, Kuang [7] Adams, Mark J. [8] Renteria, Miguel E. [9] Feng, Yan [1] [2] Gaziano, J. M. [10] [11] [12] [13] [14] [15] Stein, Dan 0000-0001-7218-7810 Zar, Heather J. [6] Campbell, Megan L. 0000-0002-6295-5254 [6] van Heel, David A. [1] [16] Trivedi, Bhavi [1] [16] Finer, Sarah [1] [16] McQuillin, Andrew 0000-0003-1567-2240 [1] [2] Bass, Nick [1] [2] Chundru, V. Kartik 0000-0002-6348-5565 [17] Martin, H. C. [17] Huang, Qin Qin 0000-0003-3073-717X [17] Valkovskaya, Maria Chu, Chia Yi [1] [2] Kanjira, Susan Kuo, Po-Hsiu [18] [19] Chen, Hsi-Chung 0000-0003-3191-0093 [18] [19] Tsai, Shih-Jen [20] [21] Liu, Yu-Li [22] Kendler, Kenneth S. [23] Peterson, Roseann E. [23] [24] Cai, Na 0000-0001-7496-2075 [25] [26] [27] Fang, Yu [28] [29] Sen, Srijan [28] [29] Scott, Laura J. [28] [29] Burmeister, Margit [28] [29] Loos, Ruth J. F. [30] [31] [32] Preuss, Michael H. [32] Actkins, Ky'Era V. [33] Davis, Lea K. [33] Uddin, Monica 0000-0001-7404-2068 [34] [35] Wani, Agaz H. [34] [35] Wildman, Derek E. [34] [35] Aiello, Allison E. [36] Ursano, Robert J. [37] Kessler, Ronald C. [11] [12] Kanai, Masahiro [11] [38] [39] [40] [41] Okada, Yukinori [11] [38] [39] [42] [43] Sakaue, Saori 0000-0003-3618-9717 [11] [12] [13] [38] Rabinowitz, Jill A. 0000-0002-3674-8032 [44] [45] Maher, Brion S. [44] [45] Uhl, George [46] [47] Eaton, William [44] [45] Cruz-Fuentes, Carlos S. [48] Martinez-Levy, Gabriela A. [48] Campos, Adrian I. [49] Millwood, I.Y [7] Chen, Zhengming [7] Li, Liming [50] Wassertheil-Smoller, Sylvia [51] [52] Jiang, Yunxuan [53] Tian, Chao [54] Martin, Nicholas 0000-0003-4069-8020 [9] Mitchell, Brittany L. [9] Byrne, E. 0000-0002-9491-7797 [49] Awasthi, Swapnil 0000-0002-9692-8123 [11] [40] [41] [55] [56] [57] Coleman, Jonathan R. I. [1] [58] Ripke, Stephan [11] [39] [55] [56] [57] Sofer, Tamar 0000-0001-8520-8860 [11] [13] [59] Guo, Yu 0000-0002-9179-0321 McIntosh, Andrew M. [8] Polimanti, Renato [14] [15] [60] Dunn, Erin C. [11] [39] [40] [41] Stein, Murray B 0000-0001-9564-2871 [14] [15] [61] [62] [63] Gelernter, Joel [4] Lewis, Cathryn M [1] [58] Kuchenbaecker, K. (Corresponding author) [1] [2] PGC MDD Working Grp China Kadoorie Biobank Collaborati 23AndMe Res Team Genes & Hlth Res Team BioBank Japan Project

Affiliations

  1. [1] Kings Coll London, Dept Med & Mol Genet, London, England
    2. [NORA names: United Kingdom; Europe, Non-EU; OECD];
  2. [2] UCL, Div Psychiat, London, England
    3. [NORA names: United Kingdom; Europe, Non-EU; OECD];
  3. [3] VA CT Healthcare Ctr, Dept Psychiat, West Haven, CT USA
    4. [NORA names: United States; America, North; OECD];
  4. [4] Yale Univ, Dept Genet, Sch Med, New Haven, CT USA
    5. [NORA names: United States; America, North; OECD];
  5. [5] Univ Barcelona, Dept Genet Microbiol & Stat, Barcelona, Spain
    6. [NORA names: Spain; Europe, EU; OECD];

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.

Data Provider: Clarivate

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