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

Xiangrui Meng, Georgina Navoly, Olga Giannakopoulou, Daniel F Levey, Dora Koller, Gita A Pathak, Nastassja Koen, Kuang Lin, Mark J Adams, 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 BassV Kartik Chundru, Hilary C Martin, Qin Qin Huang, Maria Valkovskaya, Chia-Yi Chu, Susan Kanjira, 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 J Scott, Margit Burmeister, Ruth J F Loos, Michael H Preuss, Ky'Era V Actkins, Lea K Davis, Monica Uddin, Agaz H Wani, Derek E Wildman, Allison E Aiello, Robert J Ursano, Ronald C Kessler, Masahiro Kanai, Yukinori Okada, Saori Sakaue, Jill A Rabinowitz, Brion S 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, Swapnil Awasthi, Jonathan R I Coleman, Stephan Ripke, PGC-MDD Working Group, China Kadoorie Biobank Collaborative Group, the 23andMe Research Team, Genes and Health Research Team, BioBank Japan Project, Tamar Sofer, Robin G Walters, Andrew M McIntosh, Renato Polimanti, Erin C Dunn, Murray B Stein, Joel Gelernter, Cathryn M Lewis, Karoline Kuchenbaecker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
JournalNature Genetics
Early online date4 Jan 2024
DOIs
Publication statusE-pub ahead of print - 4 Jan 2024

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