The principal strength of this study is the increased power obtained from the analysis of three large independent cohorts. This has allowed the examination of the effects of variants and regions that have been identified previously to determine whether they maintain an effect on depression. We have used variant-based analyses to calculate heritability enrichment across different brain regions and then also applied a complimentary approach using the genes assigned to functional gene-sets, with both methods highlighting the importance of the prefrontal brain regions. Our study highlights a number of potential gene targets for drug repositioning; however, due to the causal heterogeneity of depression, it is likely that stratifying depression will lead to clearer distinction between depression subtypes and potential treatments.
