In this work, we demonstrate that incorporation of age-at-onset of smoking into a model that allows for moderation of genetic effects in predicting nicotine dependence results in improved SNP discovery using a variety of metrics, compared with a model that did not allow for such moderation. This effect seems to be specific to age-at-onset of regular smoking, which was selected based on the results of experimental studies in animal models (Trauth et al. 2000; Trauth et al. 2001; Rodd-Henricks et al. 2002; Rodd-Henricks et al. 2002; Slotkin 2002; Adriani et al. 2004; Slotkin et al. 2008; Slotkin et al. 2009); other age-at-onset variables did not exhibit similar effects, despite being correlated with rAOS. Finally, in a multi-locus prediction, the interaction model exhibited greater predictive power than did the main-effect model with a comparable number of loci.
