Consistent with prior research (Dick et al., 2005), there was no evidence for a direct effect of GABRA6 rs3811995 on problematic alcohol use. Yet, there was support for the role of behavioral control and externalizing behavior as mediators in the association between GABRA6 rs3811995 and substance use. Those carrying the CC genotype were rated as having lower behavioral control. This corresponds to increasing support for the role of GABAergic neurotransmission, along with self-control and impulsivity (Boy et al., 2011), especially during adolescence (Silveri et al., 2013). In turn, lower behavioral control was associated with higher rates of externalizing behavior, which then predicted increased rates of substance use. These findings are consistent with prior work demonstrating that associations between GABRA6 variants and alcohol dependence only emerged among those diagnosed with dissocial personality disorder (Sander et al., 1999), which include symptoms of impulsivity and failure to plan ahead. In fact, the authors conclude that GABRA6 variants likely reflect a predisposition to antisocial behavior rather than a direct effect on alcohol dependence (Sander et al., 1999). As such, risk associated with GABRA6 variants may be due to early difficulties in controlling impulses.
