Despite no individual SNP being genome-wide significant in the EA GWAS, one gene was genome-wide significant (P2RX6, p=7.11E-07; threshold Psignificance = 2.82E-06 for 17,757 coding genes; Supplemental Table S4). The Purinergic receptor P2X 6 (P2RX6) is expressed in brain tissue, although less robustly than in musculo-skeletal tissue (Supplemental Figure S10). In addition, 4 curated gene-set terms were statistically significant (Supplemental Table S5 for individual genes in the set). These gene sets were derived from Reactome and reflected gene sets involved in signal transduction (sets 1 and 2) and hemostasis (sets 3 and 4). When the correlation between ANYDEP and imputed, genetically-regulated gene expression was tested in the EA sample using S-PrediXcan, no genes met the multiple testing corrections; however, P2RX6 was the most significant gene, with p = 3.91e-05 in the putamen basal ganglia tissue model.
