PROSPER Intervention Effects on Adolescents' Alcohol Misuse Vary by GABRA2 Genotype and Age.
- Authors
- Russell, Michael A; Schlomer, Gabriel L; Cleveland, H Harrington; Feinberg, Mark E; Greenberg, Mark T; Spoth, Richard L; Redmond, Cleve; Vandenbergh, David J
- Year
- 2018
- Journal
- Prevention science : the official journal of the Society for Prevention Research
- PMID
- 28185103
- DOI
- 10.1007/s11121-017-0751-y
- PMCID
- PMC5552492
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.
In-School Survey Total Participation by Wave**Reprinted from Preventive Medicine, Vol. 56, Spoth, R., Redmond, C., Shin, C., Greenberg, M., Feinberg, M., & Schainker, L., PROSPER community–university partnership delivery system effects on substance misuse through 6-1/2years past baseline from a cluster randomized controlled intervention trial, p. 190–196, Copyright (2013), with permission from Elsevier.
Age-varying GxI: Treatment condition reduced alcohol misuse for adolescents with the TT genotype but not for A allele carriersTVEM-estimated treatment condition simple effect sizes (IRRs, bolded lines) and 95% confidence limits (dashed lines) are presented as a continuous function of age for adolescents with the GABRA2 TT genotype (left panel), and for adolescents carrying the A allele (right panel). The flat lines in both panels at IRR=1 are reference lines against which to compare the age-varying regression coefficients. Effects are declared significant at all ages where their 95% confidence intervals do not include IRR=1. The difference in intervention condition effects on alcohol misuse between TT genotype and A allele carriers was most pronounced between ages 13 and 16, as the confidence intervals between the two groups do not overlap during these ages.
Age-varying alcohol use levels by intervention status and GABRA2 genotypeTVEM estimated alcohol use means (and 95% confidence limits) for control and intervention adolescents are shown as a continuous function of age, presented separately for adolescents with the GABRA2 rs279845 TT genotype (left panel) and adolescents carrying the A allele of GABRA2 rs279845 (right panel). Confidence intervals for alcohol misuse levels did not overlap between TT control and TT intervention youth from ages 13–16, suggesting that random assignment to the intervention condition reduced alcohol misuse for TT youth most strongly during these ages.
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