Fourth, we focused on main effects of rs1799971 to limit multiple testing. Thus, we did not examine gene-environment interactions (e.g., sex-specific effects) or gene-gene interactions. We did adjust statistically for sex, which showed no evidence for a main effect on general substance dependence (p = 0.57). Interactions likely have roles in a complex trait such as addiction, and could attenuate the genetic main effect when not accounted for (e.g. when the effect occurs only in a specific stratum). Thus, it is possible that the modest main effect that we detected could translate to a stronger effect if particular genetic or environmental backgrounds are considered. Future work could examine interactions nominated in the literature (Mague et al. 2009; Miranda et al. 2013; Ray et al. 2006).
