Implications of Genetic Variance for Substance Use Interventions in Adolescence

The goal of this project is to identify the role of specific genes in conditioning the effect of both preventative interventions and experiences in the family and peer domains through which such interventions are designed to affect adolescent outcomes. With the addition of participants' genes, PROSPER’s combination of a prospective randomized design, detailed annual assessments of both substance use outcomes and family and peer domains, and the proposed sample size (N = 3,000) will provide a unique opportunity to investigate potential interactions among genes and environments (abbreviated GxE) that may explain why preventative interventions’ effectiveness varies across individuals.

The project has three aims:

(1) Examine impact of specific genetic risk on modifying the effects of preventive interventions on the development of substance use behaviors. Published data and recent analyses indicate that participants in the intervention condition demonstrate lower rates of drug use through at least 10th grade, with effects growing over time. Moreover, 6th grade differences in youth – including characteristics that have shown significant heritabilities (i.e., delinquency and early use of gateway substances) – predict the degree of benefit gained from interventions assessed at the 10th grade follow-up, with the high risk sub-sample chosen in 6th grade showing the greatest intervention benefit supporting the plausibility of gene-by-environment interactions involving intervention experiences.

(2) Characterize the interplay between proximal environmental measures (parent-child relationship quality, parental monitoring, peer micro-environments) and specific genes on substance use and abuse during adolescence and early adulthood. We will also explore G-E correlations (rGE), proposing that the associations between family factors, such as harsh and inconsistent parenting, and substance use will vary by genotypes. Moreover, we expect that different aspects of adolescents’ environments will transact with specific genes as they co-act to influence different substance use behaviors, especially the peer contexts.

(3) Examine how GxE and rGE processes involved in substance use outcomes change from early adolescence to early adulthood and from initiation through addictive use. These changes can result in different patterns of rGE and GxE over adolescent development and into early adulthood. For example, during early adolescence family factors, such as parental monitoring, may play important roles in GxE; However, we expect that across adolescence, peers will have an increasing role in both GxE and rGE transactions.