In this study, we used two tightly coupled approaches, ASE analysis together with a high-throughput reporter assay, as an innovative strategy to discover the roles of cis-acting variants on gene regulation in AUD. We identified 88 genes whose ASE differed between AUD and control subjects in at least one of four brain regions; many of the differences were consistent in direction across brain regions. Pathway analysis showed enrichment of these genes in pathways related to neurological disorders and neurodegenerative diseases. High-throughput screening in SH-SY5Y and SK-N-BE(2) cell lines identified 53 and 130 SNPs in the 3′UTR of these genes, respectively, that showed significant ASE, among which 25 SNPs lead to ASE in the same direction in both cell lines.
