To explore the biological implications of our findings we used DEPICT to derive tissue enrichment, gene-set enrichment, and gene predictions (Supplementary Table 3) for SNPs with a p-value less than 1×10−5 in the meta-analysis. While identification of the functional variant or gene is not straightforward many of the top associations in our dataset appear in or near transcription factors with known CNS developmental functions (for additional gene predictions from DEPICT and functional annotation for each region see Supplementary Table 4). Gene-set enrichment analysis prioritized the MEIS2 subnetwork (pval= 2.30×10−6). MEIS2 is a TALE homeodomain transcription factor known to function in development. While most studies implicate MEIS2 in peripheral tissue development, recent studies have shown a role for MEIS2 regulated pathways in neurogenesis through interactions with Pax6, as well as interactions with Pax3 and Pax716,17. Notably, our analysis identified significant associations with MDD in the MEIS2, PAX6, and PAX5 regions (pval= 2.04×10−8, 3.94×10−7, and 2.59×10−5 in the 23andMe Discovery dataset). Tissue enrichment analysis showed an over-representation of central nervous system, with 12 of the 19 nominally associated tissues being from different
