We tested the age-varying interaction between GABRA2 (SNP rs279845) genotype and random assignment to the PROSPER preventive interventions predicting alcohol misuse across adolescence in a large sample of rural youth. We found an age-varying GABRA2 x Intervention that was significant from ages 12–18. For youth with the TT genotype, the intervention significantly reduced alcohol misuse whereas no significant reduction was found for A allele carriers at any age. The difference in intervention effects by GABRA2 genotype was most pronounced from ages 13–16, when confidence intervals of group-specific functions did not overlap. In the control group, TT genotype youth showed higher levels of alcohol misuse throughout adolescence, whereas in the intervention group, TT youth showed lower levels of early adolescent misuse (ages 13–16) compared to A carriers. Taken together, these results suggest that preventive interventions targeting goal-setting, decision-making, peer group affiliation, parent-child relationships, and family functioning can reduce the risk of alcohol misuse among adolescents with the GABRA2 TT genotype, especially during early to mid-adolescence, a crucial window for the prevention of future alcohol abuse or dependence. Moreover, these results provide
