Polygenic Score × Intervention Moderation: an Application of Discrete-Time Survival Analysis to Model the Timing of First Marijuana Use Among Urban Youth
- 484 Downloads
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.
KeywordsSurvival analysis Polygenic Universal intervention
This work used data from the Center for Prevention and Early Intervention at the Johns Hopkins Bloomberg School of Public Health. We are grateful for the collaboration of the Baltimore City Public Schools, teachers, parents, and students who participated in the study.
Compliance with Ethical Standards
This research was supported by grants to Nicholas Ialongo from the National Institute of Mental Health (MH57005, T32 MH18834) and the National Institute on Drug Abuse (R37DA11796, R01DA036525).
Conflict of Interest
The authors declare that they have no conflict of interest.
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.
Informed consent was obtained from all individual participants included in the study. The Institutional Review Board at the Johns Hopkins Bloomberg School of Public Health approved the study.
- Brody, G. H., Beach, S. R. H., Philibert, R. A., Chen, Y.-f., & Murray, V. M. (2009). Prevention effects moderate the association of 5-HTTLPR and youth risk behavior initiation: Gene × environment hypotheses tested via a randomized prevention design. Child Development, 80, 645–661. doi: 10.1111/j.1467–8624.2009.01288.x.CrossRefPubMedGoogle Scholar
- Brody, G., Chen, Y., Yu, T., Beach, S. R. H., Kogan, S. M., Simons, R. L., Windle, M., & Philibert, R. A. (2012). Life stress, the dopamine receptor gene, and emerging adult drug use trajectories: A longitudinal, multilevel, mediated moderation analysis. Development & Psychopathology, 24, 941–951.CrossRefGoogle Scholar
- Canter, L., & Canter, M. (1991). Parents on your side: A comprehensive parent involvement program for teachers. Santa Monica: Lee Canter & Associates.Google Scholar
- Guan, Y.-F., Li, G.-R., Wang, R.-J., Yi, Y.-T., Yang, L., Jiang, D., & Peng, Y. (2012). Application of next-generation sequencing in clinical oncology to advance personalized treatment of cancer. Chinese Journal of Cancer, 31, 463–470. doi: 10.5732/cjc.012.10216.
- Ialongo, N. S., Werthamer, L., Kellam, S. G., Brown, C. H., Wang, S., & Lin, Y. (1999). Proximal impact of two first-grade preventive interventions on the early risk behaviors for later substance abuse, depression, and antisocial behavior. American Journal of Community Psychology, 27, 599–641.CrossRefPubMedGoogle Scholar
- Kellam, S. G., Brown, C. H., Poduska, J. M., Ialongo, N., Wang, W., Toyinbo, P., Petras, H., Ford, C., Windham, A., & Wilcox, H. C. (2008). Effects of a universal classroom behavior management program in first and second grades on young adult behavioral, psychiatric, and social outcomes. Drug Alcohol Dependance, 95, S5–S28. doi: 10.1016/j.drugalcdep.2008.01.004.CrossRefGoogle Scholar
- Kellam, S. G., Wang, W., Mackenzie, A. C., Brown, C. H., Ompad, D. C., Or, F., & Windham, A. (2014). The impact of the Good Behavior Game, a universal classroom-based preventive intervention in first and second grades, on high-risk sexual behaviors and drug abuse and dependence disorders into young adulthood. Prevention Science, 15, 6–18.CrossRefPubMedCentralGoogle Scholar
- Masyn, K.E. (2014). Discrete-time survival analysis in prevention science. In Z. Sloboda, & H. Petras (Eds.), Defining prevention science, Advances in prevention science, (513–535). New York, NY: Springer Science + Business Media. doi: 10.1007/978-1-4899-7424-2_22.
- Musci, R., Masyn, K., Maher, B., Benke, K., Uhl, G., & Ialongo, N. (2015b). The effects of the interplay of genetics & early environmental risk on the course of internalizing symptoms from late childhood through adolescence. Development & Psychopathology. Google Scholar
- Musci, R., Uhl, G., Maher, B., & Ialongo, N. (2015c). Testing gene x environment moderation of tobacco and marijuana use trajectories in adolescence and young adulthood. Journal of Consulting & Clinical Psychology. Google Scholar
- Muthén, B., & Muthén, L. (1998–2013). Mplus users guide. Los Angeles: Author.Google Scholar
- Pacula, R. L. (2010). Examining the impact of marijuana legalization on marijuana consumption.Google Scholar
- Patterson, G.R., Reid J., & Dishion, T. (1992). A social learning approach: IV. Antisocial boys. Eugene, OR: Castalia.Google Scholar
- Petras, H., Schaeffer, C. M., Ialongo, N., Hubbard, S., Muthén, B., Lambert, S. F., & Kellam, S. (2004). When the course of aggressive behavior in childhood does not predict antisocial outcomes in adolescence and young adulthood: An examination of potential explanatory variables. Development and Psychopathology, 16, 919–941.CrossRefPubMedGoogle Scholar
- Petras, H., Masyn, K., & Ialongo, N. (2011). The developmental impact of two first grade preventive interventions on aggressive/disruptive behavior in childhood and adolescence: An application of latent transition growth mixture modeling. Prevention Science, 12, 300–313.CrossRefPubMedPubMedCentralGoogle Scholar
- Tapper, A. R., Nashmi, R., & Lester, H. A. (2006). Neuronal nicotinic acetylcholine receptors and nicotine dependence. In B. K. Madras, C. M. Colvis, J. D. Pollock, J. L. Rutter, D. Shurtleff, & M. von Zastrow (Eds.), Cell biology of addiction (pp. 179–190). Cold Spring Harbor: Cold Spring Harbor Laboratory Press.Google Scholar
- Uhl, G. R., Drgon, T., Johnson, C., Walther, D., David, S. P., Aveyard, P., Murphy, M., Johnstone, E. C., & Munafo, M. R. (2010b). Geomone-wide association for smoking cessation success: Participants in the Patch in Practice trial of nicotine replacement. Pharmacogenomics, 11, 357–367.CrossRefPubMedPubMedCentralGoogle Scholar
- Uhl, G., Walther, D., Musci, R., Fisher, C., Anthony, J., Storr, C., Behm, F., Eaton, W., Ialongo, N., & Rose, J. (2014). Smoking quit success genotype score v1.0 predicts quit success and distinct patterns of developmental involvement with common addictive substances. Molecular Psychiatry, 19, 50–54. doi: 10.1038/mp.2012.155.CrossRefPubMedGoogle Scholar
- Wang, Y., Browne, D., Petras, H., Stuart, E., Wagner, F., Lambert, S., Kellam, S., & Ialongo, N. (2009). Depressed mood and the effect of two universal first grade preventive interventions on survival to the first tobacco cigarette smoked among urban youth. Drug and Alcohol Dependence, 100, 194–203.CrossRefPubMedGoogle Scholar
- Wang, Y., Storr, C., Green, K., Zhu, S., Stuart, E., Lynne-Landsman, Petras, H., Kellam, S., & Ialongo, N. (2012). The effect of two elementary school-based prevention interventions on being offered tobacco and the transition to smoking. Drug & Alcohol Dependence, 120, 202–208.CrossRefGoogle Scholar