The enrichment results are reassuring, and, as we describe later, we can use our list of xQTL SNPs to enhance susceptibility locus discovery in GWAS studies. Investigators can also confidently use our xQTL lists to annotate GWAS SNPs related to the brain or nervous system which will accelerate the transition to functional studies. For example, we used our eQTLs to map the 21 SNPs (and correlated SNPs in LD with r2 > 0.8) reported in the IGAP AD GWAS and identified four candidate AD genes that are absent from the reported gene list defined by proximity36 (MADD, MTCH2, PILRA, and POLR2E). The TSS of these eQTL mapped genes were >100Kb, on average, from their respective AD SNPs. MTCH2, PILRA, and POLR2E have also been found in recent eQTL mapping studies40, demonstrating the robustness of our results. MADD has not been previously reported in this context but is a good candidate given that its expression correlates with neuronal cell death in AD41 and that it has also been reported to modulate AD-related tau toxicity in a Drosophila model42.
