It is noteworthy from a methodological standpoint that the complex nature of these findings emerged only when gender-specific interactions were examined. The two-way interactions between genotype and the hassles and uplifts scales revealed no significant moderating effects of social environment, underestimating the influence of both genotype and social environment. Moreover, the two-way interactions masked the most important finding—namely, that the gendered nature of etiological pathways produced very different GxE patterns in alcohol dependence for men and women. Thus, gender differences in GxE effectively washed out this effect, leading to an underestimation of this effect and a Type II error. These results underscore the critical need to consider gender-specific pathways in GxE research, supporting the need for complex models that move beyond the interaction of genotype and only one indicator of the social environment (Shanahan and Hofer 2005). In other words, the role of the environment in moderating the phenotypic expression of genotype is complicated by genetic or social heterogeneity that influences gene–environment interactions (i.e., GxExE).
