We used the results of GWA studies of Bipolar Disorder (GAIN and TGen) 11, 12 in order to evaluate whether incorporating a priori functional (mQTL) information into GWA studies would have utility for increasing power to detect significant associations. The meta-analysis of the original GWA studies yielded no genome-wide significant findings 11, 12. But restricting the association analysis to cis mQTLs (p < 0.001, n=59959) identified a SNP, rs12618769, that acts locally to regulate methylation patterns for INPP4A (p = 0.0009) and exhibits significant association (TGen+GAIN, p = 8.318e-07, OR=1.43, T allele) with Bipolar Disorder that can survive Bonferroni correction for 59959 tests. We also found the SNP was a cis eQTL for UNC50 (p = 0.009). In the WTCCC study 13, the SNP showed a replicated association at p = 0.02 (OR=1.14, T allele). If we restrict the association analyses to cis mQTLs-cis eQTLs (i.e., SNPs affecting both methylation and expression regardless of the target gene), the SNP rs12618769 continues to be significant with the number of tests reduced to 18173.
