The Pennsylvania State University, 404 Health and Human Development Building, University Park, PA, 16802, USA.
University at Albany, State University of New York, Albany, NY, USA.
Prev Sci. 2018 Jan;19(1):27-37. doi: 10.1007/s11121-017-0751-y.
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.
预防干预对青少年酗酒的影响可能因基因与干预（G×I）相互作用中的基因型而异，而这些 G×I 相互作用可能随年龄的变化而变化。本研究采用一种新的统计方法，即时变效应模型（TVEM），检验了 GABRA2 基因（rs279845）单核苷酸多态性与预防干预在青少年纵向研究（年龄 11-20 岁）中预测酗酒的相互作用。预防干预措施是 PROSPER，这是一种基于社区的家庭和学校项目提供系统，从一系列基于证据的干预措施中选择。TVEM 结果显示，在 12 至 18 岁之间存在 GABRA2 与干预的显著时变相互作用，最大效应大小出现在 13 岁左右（IRR=0.50）。该干预措施显著降低了 GABRA2 TT 基因型青少年在 12.5 至 17 岁期间的酗酒行为，但在任何年龄段都没有降低 GABRA2 A 等位基因青少年的饮酒量。GABRA2 基因型的干预效果差异在 13 至 16 岁时最为明显，这一时期饮酒与酒精使用障碍的风险增加有关。我们的研究结果提供了额外的证据，表明预防干预对青少年酗酒的影响可能因基因型而异，并提供了新的证据表明 GABRA2 与干预对饮酒的影响之间的相互作用可能随年龄而变化。讨论了针对青少年酗酒的干预措施的含义。
