The selected environmental exposure must be predictive of phenotype variability60. This point is straightforward, but should be extended to take into consideration the specific subgroup being studied. In order to examine the inter-relationships between genetic and environment effects, a predisposing or protective environment must be selected that varies in the targeted population group. For instance, while protective effects for religion are widely documented for African Americans67–69, as well as Latinos/Hispanics and Whites70, genetic studies of AUD that include highly-religious subgroups, such as rural and Southern African Americans or immigrant and first-generation Latinas, should carefully assess whether respondents have had enough exposure to alcohol to test G–E relationships. Certain religious affiliations (such as Southern/American Baptist, conservative Protestant, fundamentalist Christian, Mormon, Muslim, and others) are strongly associated with abstinence from alcohol71.
