This study describes a meta-analysis of the three largest depression cohorts (total n = 807,553, with 246,363 cases and 561,190 controls) currently available. The meta-analysis identified 102 independently-segregating genetic variants associated with depression in 101 loci and demonstrated a consistency of effect directionality in a large replication sample (total n = 1,306,354, with 414,055 cases and 892,299 controls) and across the three contributing studies allowing greater confidence in the findings. The heritability enrichments and gene-set analysis both provided evidence for the role of prefrontal brain regions in depression and the genes identified contribute to our understanding of biological mechanisms and potential drug targeting opportunities. These findings advance our understanding of the underlying genetic architecture of depression and provide novel avenues for future research.
