The brain-signaling molecule (i.e., neurotransmitter) γ-aminobutyric acid (GABA), by interacting with a molecule called the GABA-A receptor, mediates several effects of alcohol, including alcohol’s sedative and anxiety-reducing (i.e., anxiolytic) effects, motor incoordination, tolerance, and dependence (Kumar et al. 2009). Several genes that encode subunits of the GABA-A receptor are associated with an increased risk for alcoholism. For example, significant evidence suggests that a gene called GABRA2, which with other GABA-A receptor genes is located in a cluster on chromosome 4, is associated with alcoholism (Edenberg et al. 2004). This finding has been replicated in many (but not all) case–control studies in Europeans, Australians, and Plains Indians (Edenberg and Foroud 2006; Gelernter and Kranzler 2009). In several samples, the association with GABRA2 was greatest among those alcohol-dependent people who also were dependent on nicotine (Philibert et al. 2009) or illicit drugs (Agrawal et al. 2006; Philibert et al. 2009); the latter subgroup is characterized by greater severity of alcohol problems in general (Dick et al. 2007). In addition, another gene within the chromosome 4 GABA-A cluster, GABRG1, also may influence the risk for alcoholism (Covault et al. 2008; Enoch et al. 2009).
