Functional support for the SNPs with the strongest evidence of association in the trio-case-control meta-analysis was sought by determining effects of the most significantly associated SNPs (p<0.001) on both gene expression (expression quantitative trait loci- eQTLs) and on methylation level (methylation quantitative trait loci-mQTLs). This was done with eQTLs from frontal lobes,53 parietal lobes,53 lymphoblastoid cell lines (LCL),54 and the cerebellum,54 and with mQTLs54 from cerebellum, using previously collected data.54 To test whether the SNPs with the strongest observed associations were enriched for eQTLS or mQTLs, the LD-independent SNPs from the trio-case-control analyses with p<0.001 and with p<0.01 were compared to 1,000 random sets of the same size, conditioning on allele frequency, to yield an empirical distribution. An enrichment p-value was then calculated as the proportion of randomized sets in which the eQTL (or mQTL) count matched or exceeded the actual observed count in the list of top SNP associations, as previously described53 (see Supplementary materials).
