There are several interrelated conceptual and methodological challenges in cGxE research. Perhaps the biggest challenge when incorporating measured genotypic data into behavioral studies is the question of, “Which gene?” Typically, in the behavioral sciences, a single variant in a handful of “usual suspect” candidate genes that have a purported biological function or are hypothesized to confer sensitivity to one’s environment are examined (e.g., SLC6A4, MAOA, DRD2, DRD4, and COMT). For example, Schlomer et al. selected DRD4 on the basis that variation in this gene has been previously associated with sensitivity to one’s environment. This approach for candidate gene selection is popular; however, it is problematic, for a few reasons. First, history has shown that we have not been very good at identifying plausible candidate genes that confer risk for behavioral outcomes (e.g., internalizing or externalizing behaviors), and very few well-replicated associations have emerged from these hypothesized genes of interest (Bosker et al., 2011; Collins, Kim, Sklar, O’Donovan, & Sullivan, 2012). Exceptions to this include variants in the alcohol dehydrogenase (ADH) gene cluster and alcohol outcomes (Gelernter et al., 2013; Thomasson
