Since many of the top signals in the primary meta-analysis (p<0.001) appeared to lie within or adjacent to known brain-expressed genes (Table S2), we sought functional evidence to support the observed associations by evaluating the effect of these SNPs on transcriptional expression and DNA methylation levels. We annotated all GWAS SNPs with expression QTL (eQTL) information derived previously from lymphoblast cell lines (LCLs), adult cerebellum, and frontal cortex as well as methylation QTL (mQTL) information from adult cerebellum (Table S2). The top LD-independent SNPs (412 SNPs with p<0.001) were subsequently tested for eQTL and mQTL enrichment. These top SNPs from the primary analysis were nominally enriched for eQTLs in frontal cortex (empirical p-value=0.045) with a trend toward enrichment in cerebellum (p=0.077), but no enrichment in LCLs (p=0.712) (Figure 2a-c). The highest association signals were also nominally enriched for cerebellar mQTLs (p=0.011) (Figure 2d). A similar test for SNPs located within gene loci found no enrichment (p=0.258), though missense SNPs demonstrated a borderline enrichment (p=0.098).
