ArticleArXiv2026
Time-Varying Environmental and Polygenic Predictors of Substance Use Initiation in Youth: A Survival and Causal Modeling Study in the ABCD Cohort.
Article in ArXiv, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Early initiation of alcohol, nicotine, cannabis, and other substances is a robust predictor of later substance use disorders and related psychopathology. We integrate time-varying environmental factors with polygenic risk scores (PRS) in a longitudinal framework to identify risk factors influencing substance initiation in adolescents. Methods: We analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study Results: In univariate models, earlier initiation was broadly associated with multiple time-varying variables, including impulsivity and externalizing behaviors, sleep disturbance, parenting and monitoring, medication and caffeine use, school functioning and absenteeism, and cultural or value-based measures, alongside other mental health and behavioral factors. In multivariable Cox models, a smaller subset of environmental predictors remained robustly associated with the hazard of initiation across alcohol, nicotine, cannabis, and any substance, highlighting consistent signals in impulsivity traits, parental monitoring, and select health and lifestyle factors. PRS for alcohol use disorder (AUD), cannabis use disorder (CUD), nicotine dependence, and any SUD were positively associated with earlier initiation (hazard ratio [HR] > 1), with the strongest and most consistent signal observed for nicotine PRS (e.g., alcohol initiation HR ≈ 2.37; any-substance initiation HR ≈ 2.98). AUD PRS showed weaker associations for alcohol initiation but stronger associations for any-substance initiation. Causal analyses suggested that parental monitoring (PMQ mean), UPPS lack of planning, UPPS sensation seeking, and caffeine exposure may influence time to initiation: higher parental monitoring was protective (odds ratio [OR] ≈ 0.33-0.64), whereas higher impulsivity traits and caffeine exposure were associated with increased risk (OR ≈ 1.47-3.87) across outcomes, with conclusions robust across weighting specifications. Conclusions: Integrating time-varying environmental predictors with polygenic risk in a survival framework helps identify environmental factors most strongly associated with earlier substance use initiation beyond genetic liability. Follow-up causal analyses further highlight potentially actionable pathways, particularly parenting and monitoring and impulsivity-related traits, that may contribute to the developmental trajectory leading to adolescent substance use disorders.
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41994173PMC13082135What OpenQuestion holds
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