Abstract

Deciphering the genetic architecture of depression is pivotal for characterizing the associated pathophysiological processes and development of new therapeutics. Here we conducted a cross-ancestry genome-wide meta-analysis on depression (416,437 cases and 1,308,758 controls) and identified 287 risk loci, of which 49 are new. Variant-level fine mapping prioritized potential causal variants and functional genomic analysis identified variants that regulate the binding of transcription factors. We validated that 80% of the identified functional variants are regulatory variants, and expression quantitative trait loci analysis uncovered the potential target genes regulated by the prioritized risk variants. Gene-level analysis, including transcriptome and proteome-wide association studies, colocalization and Mendelian randomization-based analyses, prioritized potential causal genes and drug targets. Gene prioritization analyses highlighted likely causal genes, including TMEM106B, CTNND1, AREL...

Authors	Li, Y; Dang, X; Chen, R; Teng, Z; Wang, J; Li, S; Yue, Y; Mitchell, BL; Zeng, Y; Yao, YG; Li, M; Liu, Z; Yuan, Y; Li, T; Zhang, Z; Luo, XJ
Journal	NATURE HUMAN BEHAVIOUR
Pages
Volume
Date	24/03/2025
Grant ID	U2102205 | National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund); 82301690 | National Natural Science Foundation of China (National Science Foundation of China)
Funding Body
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/s41562-024-02073-6