An early GxE study found that greater religiosity diminished latent genetic influences on alcohol use initiation14. Since then, genetically informed resilience research has identified several aspects of religiosity as important protective factors against substance use behaviors15–17, which may limit the expression of genetic propensity for CUD. This can be interpreted in the context of Shanahan and Hofer’s social context as social control5, which refers to protective environments that may attenuate a genetic predisposition toward a negative outcome. In contrast, contextual triggering5 was used to describe a detrimental environment combining with a genetic predisposition toward a negative outcome. For example, adverse experiences have been shown to exacerbate genetic influences on substance use and disorders18–20, including CUD17,21,22. We note that even the association of Alcohol Dehydrogenase 1B (Class I), Beta Polypeptide (ADH1B)-rs1229984 with alcohol use/problems, and Cholinergic Receptor Nicotinic Alpha 5 Subunit (CHRNA5)-rs16969968 with cigarette smoking, two of the most robust and replicable genetic effects in the substance use literature, have been found to differ as a function of trauma exposure13,23,24. However, critiques of early GxE studies pointed to the likelihood of
