Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.
Meng X., Navoly G., Giannakopoulou O., Levey DF., Koller D., Pathak GA., Koen N., Lin K., Adams MJ., Rentería ME., Feng Y., Gaziano JM., Stein DJ., Zar HJ., Campbell ML., van Heel DA., Trivedi B., Finer S., McQuillin A., Bass N., Chundru VK., Martin HC., Huang QQ., Valkovskaya M., Chu C-Y., Kanjira S., Kuo P-H., Chen H-C., Tsai S-J., Liu Y-L., Kendler KS., Peterson RE., Cai N., Fang Y., Sen S., Scott LJ., Burmeister M., Loos RJF., Preuss MH., Actkins KV., Davis LK., Uddin M., Wani AH., Wildman DE., Aiello AE., Ursano RJ., Kessler RC., Kanai M., Okada Y., Sakaue S., Rabinowitz JA., Maher BS., Uhl G., Eaton W., Cruz-Fuentes CS., Martinez-Levy GA., Campos AI., Millwood IY., Chen Z., Li L., Wassertheil-Smoller S., Jiang Y., Tian C., Martin NG., Mitchell BL., Byrne EM., Awasthi S., Coleman JRI., Ripke S., PGC-MDD Working Group None., China Kadoorie Biobank Collaborative Group None., 23andMe Research Team None., Genes and Health Research Team None., BioBank Japan Project None., Sofer T., Walters RG., McIntosh AM., Polimanti R., Dunn EC., Stein MB., Gelernter J., Lewis CM., Kuchenbaecker K.
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.