GWAS results were examined for enrichment of functional SNPs previously associated with gene expression levels in several brain regions (i.e., expression quantitative trait locus SNPs, eQTLs) or with variation in gene methylation levels (methylation QTLs, mQTLs). eQTL data were generated from cerebellum, parietal, and frontal cortex (Supplementary Methods). mQTLs were derived from adult cerebellum (24). Only GWAS SNPs meeting high stringency criteria for eQTLs or mQTLs (p<10−6) were considered. For each phenotype (TS, OCD, combined), a quantile-quantile (Q-Q) plot of GWAS disease association p-values was generated for eQTL and mQTL SNPs and compared to a standard Q-Q plot of GWAS p-values expected under the null assuming no enrichment. A leftward shift in the eQTL/mQTL Q-Q plot relative to the diagonal line (representing the null distribution) indicates enrichment of eQTLs/mQTLs. The level of enrichment of eQTLs or mQTLs in each brain tissue associated with TS or OCD was then quantified using a false discovery rate (FDR) of <0.25, i.e., 75% of observed SNPs represent true disease associations (Supplementary Methods).
