For a specific variant in the regulatory region, when the direction of the GWAS effect is in the same or opposite direction as its association with the expression of a nearby gene, the higher or lower expression level of the gene may contribute to the trait. These genes are considered risk or protective genes to AUD. We therefore compared the log2 fold change of differentially expressed genes with the GWAS effect size multiplied by the sign of the eQTL effect size of the same gene. We identified multiple genes in several cell types that had expression changes in the same direction as the GWAS*eQTL effect, including PPP2R3C in oligodendrocytes and D1/D2 MSNs (Fig. 5C-D), and ADAL in all MSNs (Fig. 5D-F). The expression of these genes was either positively associated with AUD (genes in the first quadrant) – i.e., risk genes, like ERF in oligodendrocytes – or negatively associated (genes in the third quadrant) – i.e., protective genes, such as PPP2R3C in oligodendrocytes.
