Gamma amino butyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, and its transmission is considered to mediate the pharmacological effects of alcohol in the brain. The modulatory actions of GABA are mediated through two types of receptors: the ionotropic GABAA receptor and the metabotropic GABAB receptor (57, 137). A family study from the COGA group identified multiple SNPs in GABRA2 (which encodes the GABAA receptor α2 subunit) associated with increased risk for alcohol dependence (34). Several subsequent studies using case-control samples replicated the association of GABRA2 and alcohol dependence, though the nature of the association and the specific variants associated with alcohol dependence differ in some samples (27, 40, 43, 80, 119). Furthermore, one study showed that GABRA2 alleles affect the SRE (self-rating of the effects of alcohol), suggesting that genetic variations in GABRA2 might play a role in the risk for alcohol-use disorders by moderating the SRE (111). Evidence from a functional MRI study suggested that a SNP in GABRA2 (rs279871) associated with alcohol dependence is also associated with the medial frontal response to alcohol cues (72).
