Next, we tested for sQTLs, or whether specific genetic variants were associated with the differentially spliced genes associated with AUD. In total, we found 6,463 unique sQTLs linked with 170 different genes (padj < 0.05; see Fig. 4 and Supplementary File S6). Drug metabolism (CYP2C19 and CYP2C9) intracellular signaling (GRK4, GRK6, HDAC3, PRKACB, and MAPK3K6) and calcium ion channel genes (CACNA1A, CACNA1G, CACNB2, and KCNMA1) had sQTL(s). Exon skipping events in the CACNA1A and KCNMA1 genes corresponded to certain gene formations that differentially alter vesicular release41 and activation of Ca+ channels42. Most sQTLs were located in intergenic regions (52.3%) or introns (36.1%), but we only identified sQTL enrichment among DNaseI hypersensitivity sites, enhancer regions, and downstream locations of protein-coding genes (see Fig. 4).
