The result of our cis eQTL enrichment analysis strongly demonstrates the influence of genetic regulation of gene expression in brain on Bipolar Disorder. In contrast to the enrichment method (which tests a polygenic model that includes tens of thousands of SNPs with disease association p < 0.50) utilized by a recent study 24 that reports enrichment for alleles that affect gene expression in brain among Schizophrenia susceptibility alleles, our enrichment results were robustly observed in the significant Bipolar Disorder susceptibility associations at different significance thresholds (p < 0.001 and p < 0.0001) for association with disease. Finally, through the use of local mQTL information, we identified a significant association, rs12618769, that can stand multiple testing correction for all mQTLs tested in the GWA studies of TGen+GAIN Bipolar Disorder. We found the SNP to regulate (p = 0.0009) the methylation of inositol polyphosphate phosphatase 4A (INPP4A) in cis. The gene INPP4A has been shown to protect neurons from excitotoxic cell death and to maintain the functional integrity of the brain 26. Remarkably, a previous study has shown that increased excitotoxicity may
