In addition to indirect effects, GABRA2 genotype also had a direct effect on adolescent alcohol problems that survived correction for multiple testing. Interestingly, this effect was such that those with the GG genotype had higher alcohol problems, which is opposite from the indirect effects showing that the AA/AG genotypes predicted externalizing problems through disinhibition. These effects held in models that did and did not control for T1 alcohol problems, suggesting that the switch in risk allele is not due to prediction of change in alcohol problems over 18 months. It is impressive that this GABRA2 SNP predicted change in alcohol problems over 18 months, especially given the high correlation between T1 and T2 alcohol problems. As stated earlier, the risk allele for rs279858 (as well as for other SNPs in the same haplotype block) has been inconsistent in the literature. Some studies found that the major (A) allele was associated with increased risk for externalizing phenotypes [15, 20, 28], while other studies including a meta-analysis found that the minor (G) allele was associated with increased risk for externalizing phenotypes [12, 16, 23, 25, 29].
