We focused on variation in methylation of three CpG sites in the first exon of OXTR because prior research suggested that this portion of the epigenetic signature for OXTR was associated with stress as well as with behavioral outcomes (Simons et al., in press), and because these elements cohered as a single factor. Of the four factors capturing significant variance in methylation across OXTR, only one was located on the first exon and it replicated exactly the factor previously shown to be responsive to stress and associated with behavioral outcomes (Simons et al., in press). Using this factor as our index of OXTR methylation, our regression analyses supported the hypothesized model. SAAF differentially predicted early substance use, and early substance use differentially predicted greater methylation of OXTR. Indirect effects of SAAF on methylation of OXTR were significant only for “s” allele carriers. This resulted in a significantly greater indirect effect of SAAF on OXTR methylation among carriers of the “s” allele than among those with the “ll” genotype, i.e. a pattern of moderated mediation.
