“Multi-Ancestry GWAS of Major Depression Aids Locus Discovery, Fine-Mapping, Gene Prioritization, and Causal Inference”, Xiangrui Meng, Georgina Navoly, Olga Giannakopoulou, Daniel Levey, Dora Koller, Gita Pathak, Nastassja Koen, Kuang Lin, Miguel Renteria, Yanzhe Feng, J. Michael Gaziano, Dan Stein, Heather Zar, Megan Campbell, David 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 Kendler, Roseann Peterson, Na Cai, Yu Fang, Srijan Sen, Laura Scott, Margit Burmeister, Ruth Loos, Michael Preuss, Ky’Era Actkins, Lea Davis, Monica Uddin, Agaz Wani, Derek Wildman, Robert Ursano, Ronald Kessler, Masahiro Kanai, Yukinori Okada, Saori Sakaue, Jill Rabinowitz, Brion Maher, George Uhl, William Eaton, Carlos Cruz-Fuentes, Gabriela Martinez-Levy, Adrian Campos, Iona Millwood, Zhengming Chen, Liming Li, Sylvia Wassertheil-Smoller, Yunxuan Jiang, Chao Tian, Nicholas Martin, Brittany Mitchell, Enda Byrne, Naomi Wray, Swapnil Awasthi, Jonathan Coleman, Stephan Ripke, PGCD Working Group, China Kadoorie Biobank Collaborative Group, 23andMe, Genes Health Research Team, Tamar Sofer, Robin Walters, Renato Polimanti, Erin Dunn, Murray Stein, Joel Gelernter, Cathryn Lewis, Karoline Kuchenbaecker2022-07-21 (Mendelian Randomization, depression)⁠:

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 participants (32%).

The multi-ancestry GWAS identified 190 statistically-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 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 3 → 12. A transcriptome-wide association study identified 354 statistically-significantly associated genes, 205 of them novel. Mendelian Randomization 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.