Beyond these predisposing differences in the genome, AUD is likely associated with dynamic alterations in gene expression and chromatin conformation, plausibly in brain regions associated with onset and maintenance of motivated and rewarding behaviors, stress responsivity and cognitive control. Early studies using microarray analysis to study the effects of chronic ethanol consumption in rats found significant changes in expression in genes in several brain regions, including the nucleus accumbens,8,9 extended amygdala,10,11 and ventral tegmental area,12 and studies in human lymphoblastoid cell lines and postmortem tissue identified expression changes associated with alcohol dependence.13,14 Subsequent bulk RNA-sequencing (RNA-seq) studies have uncovered differentially expressed genes in several brain regions, including the rat hippocampus, prefrontal cortex15, raphe nuclei,16 and periaqueductal gray17, in human lymphoblastoid18 and neuroblastoma19 cell lines, and in human postmortem tissue from the hippocampus,20 prefrontal cortex,21,22 and striatum.23
