Our results suggest that one possibility for the mixed findings is that GABRA2 may have more than one pathway to externalizing outcomes, which has been previously proposed and empirically observed by other researchers using adult samples [4, 69]. Using our results as an example, one pathway might be through the influence of the A/major alleles on disinhibition. Although less clear, multiple mechanism(s) might be involved in other pathways of risk. For instance, one study found that presence of the G allele of rs279858 predicted adolescent substance use through rule-breaking behaviors [12]. Interestingly, numerous studies reported associations between GABRA2 variation (including rs279858) and increased positive subjective alcohol effects [65–67], possibly because GABAA receptors undergo allosteric modulation by ethanol, benzodiazepines and barbituates [4]. Thus, perhaps the GG genotype increases risk for adolescent alcohol problems through its effect on positive subjective responses to alcohol in our sample. This is in line with our findings because we only found a direct effect of the GG genotype on adolescent alcohol problems. Note, however, that the GABRA2 risk alleles were inconsistent in the prior studies on
