Polygenic Score × Intervention Moderation: an Application of Discrete-Time Survival Analysis to Model 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., Archives of general psychiatry 60:1256–1264, 2003 ; Verweij et al., Addiction 105:417–430, 2010 ). A previous work has found a significant interaction between the polygenic score and the same elementary school-based intervention with 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., Molecular Psychiatry 19:50–54, 2014 ). Using data from a longitudinal preventive intervention study ( N = 678), we examined age of first marijuana use from sixth grade to age 18. Genetic data were collected during emerging adulthood and were genotyped using the Affymetrix 6.0 microarray ( N = 545). 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 = .050). We also found a significant intervention × polygenic score interaction effect at p = .003, with participants at the higher end of the polygenic score benefiting 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.