In this review, we describe how COGA has been conducting cellular and molecular studies to understand functional mechanisms linking genes and variants identified by GWAS to the risk for AUD. These include studies on gene regulation in lymphoblastoid cells from COGA participants with and without alcohol exposure, and in post‐mortem brain tissues from individuals with or without AUD, combined with bioinformatic analyses (Figure 1). Molecular studies also use high throughput reporter assays (HTRA) to identify SNPs in which alternate alleles differ in driving gene expression. To evaluate variants with hypothesized function in the central nervous system (CNS), electrophysiology and gene expression studies are performed in neurons differentiated from induced pluripotent stem cells (iPSCs) derived from COGA participants (Figure 1). The overall goal is to exploit the robust genomic data, curated phenotypes, and banked cells from the individuals studied by COGA to identify mechanisms contributing to AUD.
