Since Edenberg et al’s original report [2], related or identical variants in GABRA2 genes have also been associated with other addictive behaviours, including cocaine abuse [10], heroin abuse [11] and polydrug abuse [12], [13]. That related haplotypes were associated with several forms of addiction make it unlikely that possession of a risk haplotype simply confers increased or decreased sensitivity to ethanol. Indeed the same variations are also associated with childhood conduct disorder [14], [15] and with increased impulsivity [16], behavioural traits that may contribute to the development of addictive behaviours. There is also emerging evidence that the influence of GABRA2 haplotypes on the development of addictions is due to an interaction with early life stress [11]. Since facilitated GABAergic transmission via α2-subunit containing receptors contributes to the anxiolytic action of benzodiazepines [17], [18] and barbiturates [19] and deletion of the α2-subunit gives rise to an anxious phenotype [19], genetic variations may contribute to the ability to cope with early life stress, and thus lead to an increased likelihood of addiction.
