Polygenic Score x Intervention Moderation: An Application of Discrete-Time Survival Analysis to Modeling the Timing of First Marijuana Use Among Urban Youth

The present study examines the interaction between a polygenic score and an elementary-school based universal preventive intervention trial and its effects on a discrete time survival analysis of time to first smoking marijuana.  Research has suggested that initiation of substances is both genetically and environmentally driven (Rhee et al., 2003; Verweij et al., 2010).  Previous work has found a significant interaction between the polygenic score and the same elementary-school based intervention with for tobacco smoking (Musci et al., in press).  The polygenic score reflects the contribution of multiple genes and has been shown in prior research to be predictive of smoking cessation, tobacco use, and marijuana use (Uhl et al., 2014).  Using data from a longitudinal preventive intervention study, we examined age of first marijuana use from 6th grade to age 18.  Genetic data were collected during emerging adulthood and were genotyped using the Affymetrix 6.0 microarray. The polygenic score was computed using these data.  Discrete time survival analysis was employed to test for intervention main and interaction effects with the polygenic score.  We found main effect of the polygenic score approaching significance, with the participants with higher polygenic scores reporting their first smoking  marijuana at an age significantly later than controls (p=.083). We also found an intervention x polygenic score interaction effect that approached significance at p = .066, with participants at the higher end of the polygenic score benefitting the most from the intervention in terms of delayed age of first use.  These results suggest that genetics may play an important role in the age of first use of marijuana and that differences in genetics may account for the differential effectiveness of classroom-based interventions in delaying substance use experimentation.