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Get Free AccessAbstract 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/Latinx participants (32%). The multi-ancestry GWAS identified 190 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/Latinx 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 from 3 to 12. A transcriptome-wide association study identified 354 significantly associated genes, 205 of them novel. Mendelian Randomisation 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.
Xiangrui Meng, Georgina Navoly, Olga Giannakopoulou, Daniel F. Levey, Dóra Koller, Gita A. Pathak, Nastassja Koen, Kuang Lin, Miguel E. Rentería, Yanzhe Feng, J. Michael Gaziano, Dan Joseph Stein, Heather J. Zar, Megan L. Campbell, David A. van Heel, Bhavi Trivedi, Sarah Finer, Andrew McQuillin, Nicholas Bass, V. Kartik Chundru, Hilary C. Martin, Qin Huang, Maria Valkovskaya, 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 Preuß, Ky’Era V. Actkins, Lea K. Davis, Monica Uddin, Agaz H. Wani, Derek E. Wildman, Robert J. Ursano, Ronald C. Kessler, Masahiro Kanai, Yukinori Okada, Saori Sakaue, Jill A. Rabinowitz, Brion S. Maher, George R. Uhl, William W. Eaton, Carlos S. Cruz-Fuentes, Gabriela Ariadna Martínez-Levy, Adrián 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, Naomi R. Wray, Swapnil Awasthi, Jonathan R. I. Coleman, Stephan Ripke, Tamar Sofer, Robin Walters, Renato Polimanti, Erin C. Dunn, Murray B. Stein, Joel Gelernter, Cathryn M. Lewis, Karoline Kuchenbaecker (2022). Multi-ancestry GWAS of major depression aids locus discovery, fine-mapping, gene prioritisation, and causal inference. , DOI: https://doi.org/10.1101/2022.07.20.500802.
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Type
Preprint
Year
2022
Authors
74
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1101/2022.07.20.500802
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