or mediators. When imputed SNPs are used, it is common to replace the genotype predictor with uncertainty-adjusted dosage. The use of linear mixed models (LMM) for genetic association analysis has grown rapidly in recent years to allow for valid tests of the relationship between a measured SNP and phenotypic outcome and are especially useful in prevention trials, where longitudinal data are collected (Eu-Ahsunthornwattana et al., 2014). Simpler and more complicated models can be estimated using, for example, lme4 in R (Bates, Maechler, Bolker, & Walker, 2014) with genotype predicting longitudinal methylation outcomes and/or methylation predicting subsequent behavioral outcomes. An additional advantage of using linear/logistic models is the easy extension to explore mechanisms (e.g., mediation or moderation) of discovered associations. For example, by employing the mediation package in R, specific indirect pathways wherein methylation serves as a mediator of environmental influence(s) on subsequent behavior(s) could also be tested (Tingley, Yamamoto, Hirose, Keele, & Imai, 2014).
