PROSPER Intervention Effects on Adolescents' Alcohol Misuse Vary by GABRA2 Genotype and Age

Preventive intervention effects on adolescent alcohol misuse may differ based on genotypes in gene-by-intervention (G x I) interactions, and these G x I interactions may vary as a function of age. The current study uses a novel statistical method, time-varying effect modeling (TVEM), to test an age-varying interaction between a single nucleotide polymorphism in the GABRA2 gene (rs279845) and a preventive intervention in predicting alcohol misuse in a longitudinal study of adolescents (ages 11-20). The preventive intervention was PROSPER, a community-based system for delivery of family and school programs selected from a menu of evidence-based interventions. TVEM results revealed a significant age-varying GABRA2 x intervention interaction from ages 12 to 18, with the peak effect size seen around age 13 (IRR = 0.50). The intervention significantly reduced alcohol misuse for adolescents with the GABRA2 TT genotype from ages 12.5 to 17 but did not reduce alcohol use for adolescents with the GABRA2 A allele at any age. Differences in intervention effects by GABRA2 genotype were most pronounced from ages 13 to 16-a period when drinking is associated with increased risk for alcohol use disorder. Our findings provide additional evidence that intervention effects on adolescent alcohol misuse may differ by genotype, and provide novel evidence that the interaction between GABRA2 and intervention effects on alcohol use may vary with age. Implications for interventions targeting adolescent alcohol misuse are discussed.