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Chunk #9 — Specific Hypotheses

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Prevention of Early Substance Use Mediates, and Variation at SLC6A4 Moderates, SAAF Intervention Effects on OXTR Methylation.
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We examine three main hypotheses. First, we examine the effect of SAAF on early initiation of substance use, predicting that it will be moderated by the presence of the “s” allele in the 5-HTTLPR, replicating prior analyses with the full sample. Second, we examine the effect of early initiation of substance use on methylation of OXTR in young adulthood, predicting that its impact also will be moderated by variation at the 5-HTTLPR, extending prior research on mechanisms by which genotype may influence long-term trajectories and amplify the impact of early contexts on young adult outcomes. Third, we examine the indirect effect of participation in the SAAF program on methylation of OXTR in young adulthood through prevention of early substance use. We predict that this effect will be significant only among carriers of the “s” allele at the 5-HTTLPR, and not among non-carriers, leading to a significant mediated moderation effect. In all cases we control for gender, variation in youth exposure to SES-risk, genetic ancestry, and individual differences in cell-type composition of white blood cell pellets where appropriate.