A wealth of convergent clinical and genetic data has implicated variation in GABAergic neurotransmission as a major factor in the development and maintenance of Alcohol Dependence (AD). Our understanding of GABA’s role in AD took a major leap forward in 2004 when the Collaborative Study of the Genetics of Alcoholism (COGA) group reported that genetic variation at GABRA2, a 4p13 that codes for a subunit of the GABA receptor, was associated with altered vulnerability to AD [1]. Since that time, most, but not all studies have replicated that initial finding with respect to AD [2–5] while other reports have extended the original findings to suggest that GABRA2 variability may also influence vulnerability to general drug dependence [6–8]. Taken together, these studies suggest that the GABRA2 locus has a pleiotropic effect on the risk for a broad range of substance use. Unfortunately, since many of the populations used in these studies were ascertained for alcoholism or another form of substance use, generating an unbiased understanding of the interrelationships of the substance use disorders to one another and other related behavioral illnesses such as major depressive disorder (MDD) and antisocial personality disorder (ASPD) from these data is not always possible.
