Alcohol dependence (AD) is a chronic, debilitating substance use disorder. Over the past few decades, research has unveiled the vast complexity of the genetic architecture underlying AD and alcohol-related phenotypes (ARP). Family, twin and adoption studies currently estimate the heritability of AD to be 50–60% [1, 2]. Both animal and human postmortem brain studies reveal that chronic alcohol consumption leads to broad transcriptional changes in brain regions not known to previously play a role in AD [3]. Early postmortem human brain expression studies focused on the prefrontal cortex (PFC), where genes related to GABAA receptor subunits and mitochondrial function were found to be differentially expressed in chronic alcoholics [4, 5]. Similarly, genome-wide expression studies in PFC implicated variation in the expression of genes related to processes such as myelination, cell cycling, oxidative stress, and transcription [6–11]. Research into other brain regions, such as nucleus accumbens (NAc) or the ventral tegmental area (VTA), revealed differential expression of genes related to cell architecture, cell signaling, vesicle formation, and synaptic transmission [8]. These findings suggest that there are brain region-specific susceptibilities and adaptations to chronic alcohol consumption that likely have a distinct effect on the behavioral phenotypes comprising AD [6, 8, 12].
