In this report, two nested biometric models that differ only in how cumulative AAU through age 18 is associated with P300 amplitude at age 18 are compared. The first model (“Endophenotype”) estimates the G-E influences underlying P300 amplitude as unaffected by AAU, and thus evaluates a version of the idealized model presented in Figure 1a. The second model used in this report (“Alcohol Exposure”), estimates the G-E influences underlying P300 amplitude as a function of how much alcohol was consumed by each individual. This model, by quantifying variations in the G-E interplay underlying P300 amplitude as AAU increases, is capable of detecting the types of idealized G-E variations depicted in Figures 1b and 1c as well as any other variations that might be present. Systematic change in the G-E interplay underlying P300 amplitude cannot be easily explained under the endophenotype hypothesis and, if confirmed, such moderation of P3AR would implicate alcohol consumption per se as a contributor to individual differences in P300 amplitude. In this way, biometric moderation modeling represents a novel and complementary approach to endophenotype validation.
