Some of the top candidate genes implicated in alcohol consumption in humans are transcripts for specific GABA receptor subunits (Trudell et al., 2014). An RNA-seq study compared GABAergic gene expression in human postmortem hippocampus (Enoch et al., 2012). Alcoholics had lower expression of multiple genes associated with GABA receptors; these included specific subunits for GABAA and GABAB receptors (i.e. GABBR1, GABRA2, GABRG1, GABRG2). Similar findings were reported in a separate RNA-seq study of human postmortem hippocampus (Zhou et al., 2011). The differential expression of GABA receptor subunits in human alcoholics has also been observed in the prefrontal cortex. For example, GABRA3, GABBR1, and GABBR2 were primary network contributors in human prefrontal cortex that were associated with lifetime alcohol consumption (Farris and Mayfield, 2014). A meta-analysis of candidate gene association studies also identified a strong association of the GABAA receptor subunit α2 (GABRA2) with alcohol dependence along with evidence for α6 (GABRA6) and γ2 (GABRG2) subunits (Li et al., 2014). Enoch and colleagues review earlier studies that nominated GABRA2 (Enoch et al. (2009)).
