Polygenic Score × Intervention Moderation: an Application of Discrete-Time Survival Analysis to Model the Timing of First Marijuana Use Among Urban Youth.

paper Cited Public

Authors: Musci, Rashelle J; Fairman, Brian; Masyn, Katherine E; Uhl, George; Maher, Brion; Sisto, Danielle Y; Kellam, Sheppard G; Ialongo, Nicholas S
Year: 2018
Journal: Prevention science : the official journal of the Society for Prevention Research
PMID: 27817095
DOI: 10.1007/s11121-016-0729-1
PMCID: PMC5501761

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.

#	Section	Preview
20	Method — Analysis	A discrete time survival analysis (DTSA) using Mplus Version 7.4 (Muthén & Muthén, 1998–2013)…
21	Method — Analysis	aggression and the population stratification variable were grand mean centered to ease in the…
22	Method — Analysis — Missing Data	Using full information maximum likelihood estimation, Mplus (Muthén & Muthén, 1998–2012) assumes…
23	Results — Descriptive and Univariate Statistics	Proportions of first use at each age can be seen in Table 1. The proportion of individuals…
24	Results — Survival Analysis for Marijuana First Use	A discrete time survival analysis model was ran using Mplus Version 7.1 (Muthén and Muthén,…
25	Results — Survival Analysis for Marijuana First Use	With respect to the covariates included in the model, the relationship between pre-intervention…
26	Results — Survival Analysis for Marijuana First Use	In the moderation model, an interaction term was created to measure the interaction between the…
27	Results — Survival Analysis for Marijuana First Use	An identical model was run to explore the impact of the FSP intervention of age of marijuana…
28	Discussion	The last two decades have witnessed a dramatic increase in the number of studies of the role of gene…
29	Discussion	Like in Musci et al (2016a), wherein the focus was on age of first tobacco use, we found evidence of…
30	Discussion	As noted in the introduction, our rationale for examining Uhl et al. (2010)’s quit success score…
31	Discussion	that the effect of the classroom-centered intervention on age of first cigarette smoked may have…
32	Discussion	Like in Wang et al. (2012), where no main effect of the family-school partnership intervention was…
33	Discussion	Moreover, only about a 1/3 of the parents attended more than half of the parent training workshops.…
34	Discussion	We suggested above that one of the promises of gene × intervention interaction studies was the…
35	Discussion	Further, in any analysis of gene by environment interactions, gene environment correlation is…
36	Discussion	With respect to limitations and future directions, the present study’s sample small for studies of…

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In this knowledge base

Title	Year	PMID
Psychosocial moderation of polygenic risk for cannabis involvement: the role of trauma exposure and frequency of religious service attendance.	2019	31636251
Commentary for Special Issue of Prevention Science "Using Genetics in Prevention: Science Fiction or Science Fact?".	2018	28735446

External

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A systematic review of gene-by-intervention studies of alcohol and other substance use.	Neale ZE et al.	—	2021	→
Psychosocial moderation of polygenic risk for cannabis involvement: the role of trauma exposure and frequency of religious service attendance.	Meyers JL et al.	—	2019	→
Systematic Review of Polygenic Gene-Environment Interaction in Tobacco, Alcohol, and Cannabis Use.	Pasman JA et al.	—	2019	→
Trajectories and Predictors of Children's Early-Starting Conduct Problems: Child, Family, Genetic, and Intervention Effects.	Shaw DS et al.	—	2019	→
Commentary for Special Issue of Prevention Science "Using Genetics in Prevention: Science Fiction or Science Fact?"	Dick DM	—	2018	→
Genetic moderation of the effects of the Family Check-Up intervention on children's internalizing symptoms: A longitudinal study with a racially/ethnically diverse sample.	Lemery-Chalfant K et al.	—	2018	→
The Implications of Genetics for Prevention and Intervention Programming.	Musci RJ et al.	—	2018	→