Candidate gene-by-environment research has been controversial (Duncan and Keller, 2011; Dick et al., 2015). Moving forward, focusing on genes with robust GWAS evidence is likely to yield more replicable and reliable results. In addition, the twin literature on gene environment interaction can be used to inform more targeted hypotheses about GxE effects that focus on environments shown to moderate latent genetic effects. For example, the protective effect of alcohol dehydrogenase 1B (ADH1B) was negated among individuals whose peer groups consisted of mainly drinkers (Olfson et al., 2014). The association between of the nicotinic receptor gene, CHRNA5, and nicotine dependence was stronger under conditions of low parental monitoring (Chen et al., 2009). Additionally, the effect of CHRNA5 on smoking behavior was found to be stronger among those who initiate cigarette use earlier (Hartz et al., 2012). And while marriage had a stronger protective effect on those with the low-risk genotype of GABRA2, those with the high risk genotype were less likely to enter into marriage or stay married, suggesting a process of both GxE and rGE (Dick et al. 2006c).
