Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies.

ABSTRACT: In a genome-wide association study (GWAS) meta-analysis of 688,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries across diverse and admixed ancestries, we identify 697 associations at 635 loci, 293 of which are novel. Using fine-mapping and functional tools, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. A neural cell-type enrichment analysis utilizing single-cell data implicates excitatory, inhibitory, and medium spiny neurons and the involvement of amygdala neurons in both mouse and human single-cell analyses. The associations are enriched for antidepressant targets and provide potential repurposing opportunities. Polygenic scores trained using European or multi-ancestry data predicted MD sta

SUBMITTER: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Electronic address: [e-mail] 

PROVIDER: S-EPMC11829167 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature