When combined with the prior analysis from PGC, UK Biobank, and 23andMe,10 over 1.2 million participants were available for this study, the largest genetic analysis of depression to date. We identified 178 genetic risk loci and 223 independently significant SNPs. We used the genome-wide association summary statistics from this analysis to investigate genetic correlations between depression and other cohorts with different phenotypic assessments as well as overlap with other related traits. We used genomic structural equation modeling (gSEM) to examine shared genetic architecture and pleiotropy among complex traits. We also investigated functional consequences through fine mapping analysis, transcriptomic enrichment with respect to multiple brain tissues, and functional annotation. The results provide a deep look into the genetic architecture of depression and its underlying complex biology. Finally, we replicated our findings in an entirely independent sample of 1.3 million participants from 23andMe, demonstrating the consistency of GWAS findings once adequate power is achieved.
