A powerful method to study the effects of genetic variants on gene regulation is to examine allele-specific expression (ASE). ASE measures the difference in expression between the alternative alleles and is regulated by cis-acting DNA elements, since both alleles are exposed to the same trans-acting environment in the cell. ASE analysis can be used as a marker to identify strong candidate genes with AUD-associated differential expression. ASE in genes could be influenced by several mechanisms; one is by functional variants in the 3′ untranslated regions (3′UTRs). Single nucleotide polymorphisms (SNPs) within 3′UTRs can modulate gene expression as target sites for micro-RNAs (miRNAs) or RNA-binding proteins (RBPs). A high-throughput reporter assay offers a powerful tool to screen hundreds of genomic variants associated with a specific phenotype to determine which variants affect gene regulation. The combination of ASE analysis and a high-throughput assay provides a unique strategy to uncover candidate genes contributing to AUD risk and to identify functionally relevant variants in those genes. Together, these complementary approaches provide a mechanism of action and thereby advance our understanding of the biology of AUD.
