Multi-ancestry GWAS of major depression aids locus discovery, fine-mapping, gene prioritisation, and causal inference
Author:
Meng Xiangrui, Navoly Georgina, Giannakopoulou Olga, Levey DanielORCID, Koller Dora, Pathak GitaORCID, Koen Nastassja, Lin Kuang, Rentería Miguel E.ORCID, Feng Yanzhe, Gaziano J. Michael, Stein Dan J., Zar Heather J., Campbell Megan L., van Heel David A.ORCID, Trivedi Bhavi, Finer Sarah, McQuillin Andrew, Bass Nick, Chundru V. Kartik, Martin Hilary, Huang Qin Qin, Valkovskaya Maria, Kuo Po-Hsiu, Chen Hsi-Chung, Tsai Shih-JenORCID, Liu Yu-Li, Kendler Kenneth S., Peterson Roseann E., Cai NaORCID, Fang Yu, Sen SrijanORCID, Scott Laura, Burmeister MargitORCID, Loos Ruth, Preuss Michael, Actkins Ky’Era V., Davis Lea K., Uddin MonicaORCID, Wani Agaz, Wildman Derek, Ursano Robert J., Kessler Ronald C., Kanai MasahiroORCID, Okada YukinoriORCID, Sakaue SaoriORCID, Rabinowitz Jill, Maher Brion, Uhl George, Eaton William, Cruz-Fuentes Carlos S., Martinez-Levy Gabriela A., Campos Adrian I.ORCID, Millwood Iona Y., Chen Zhengming, Li Liming, Wassertheil-Smoller Sylvia, Jiang Yunxuan, Tian Chao, Martin Nicholas G., Mitchell Brittany L., Byrne Enda M., Wray Naomi R.ORCID, Awasthi Swapnil, Coleman Jonathan R. I.ORCID, Ripke StephanORCID, Sofer TamarORCID, Walters Robin G.ORCID, Polimanti RenatoORCID, Dunn Erin C., Stein Murray B., Gelernter JoelORCID, Lewis CathrynORCID, Kuchenbaecker Karoline, , , ,
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 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.
Publisher
Cold Spring Harbor Laboratory
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