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

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Abstract

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.

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Acknowledgements

The authors would like to thank Kerry Hair, Dr. Deborah Grove, and Ashley Price of the Penn State Genomics Core Facility; Amanda Griffin of Penn State; Shirley Huck, Cathy Owen, Debra Bahr, and Anthony Connor of the Behavioral Research Services at Iowa State University Survey; and Rob Schofield and Dean Stankowski of the Penn State University Survey Research. PROSPER and gPROSPER projects were supported by grant numbers DA013709 and DA030389 from the National Institute on Drug Abuse (NIDA), respectively. The preparation of this article was supported by NIDA awards P50 DA010075 and P50 DA039838. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse or the National Institutes of Health.

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Authors and Affiliations

  1. The Pennsylvania State University, 404 Health and Human Development Building, University Park, PA, 16802, USA

    Michael A. Russell

  2. University at Albany, State University of New York, Albany, NY, USA

    Gabriel L. Schlomer

  3. The Pennsylvania State University, University Park, PA, 16802, USA

    H. Harrington Cleveland, Mark E. Feinberg, Mark T. Greenberg & David J. Vandenbergh

  4. Iowa State University, Ames, IA, USA

    Richard L. Spoth & Cleve Redmond

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  1. Michael A. Russell
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  2. Gabriel L. Schlomer
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  3. H. Harrington Cleveland
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  4. Mark E. Feinberg
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Correspondence to Michael A. Russell.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

Michael A. Russell is supported by grant numbers P50-DA010075 and P50-DA039838 from the National Institute on Drug Abuse.

This PROSPER and gPROSPER projects were supported by National Institute on Drug Abuse Grants DA013709 and DA030389, respectively.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Informed consent was obtained from all individual participants included in the study.

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Russell, M.A., Schlomer, G.L., Cleveland, H.H. et al. PROSPER Intervention Effects on Adolescents’ Alcohol Misuse Vary by GABRA2 Genotype and Age. Prev Sci 19, 27–37 (2018). https://doi.org/10.1007/s11121-017-0751-y

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