Third, multiple genomic lines of evidence support a role for MIR137 in the etiology of schizophrenia. We provide increased support for a common variant association located upstream of the MIR137 transcript (P=1.7×10−12, Supplemental Figure 13). Fourteen genes in the regions in Table 3 have miR-137 target sites predicted by TargetScan (v6.2) 43 (C6orf47, HLA-DQA1, TNXB, VARS, C10orf26, CACNA1C, DPYD, CACNB2, TSSK6, NT5DC2, PITPNM2, SBNO1, ZEB2, and PRKD3). Using gene-set analysis, we evaluated whether genes with predicted miR-137 target sites were enriched for smaller association P values. We confirmed the PGC result 17 and extended the finding by showing more robust enrichment in afar larger set of genes with predicted miR-137 target sites (Supplemental Table 7). In addition, our unpublished work shows enrichment for smaller GWAS P-values in genes down-regulated following over-expression of miR-137 in human neural stem cells (Collins, in preparation). Given the role of miR-137 in fundamental neuronal processes, 44-46 these results support investigation of pathways influenced by miR-137in regard to a role in the pathogenesis of schizophrenia.
