Several studies strongly support a general tendency to use and become dependent on multiple substances (18, 26-28). As such, we defined substance addiction phenotypically by combining dependence data across various classes of drugs. Further, because phenotypic definitions affect heritability estimates, we created three DSM-IV-based phenotypes intended to approximate those that have commonly been used in the literature. Consistent with the extant literature, we defined dependence vulnerability (DV) as a summary score based on the ratio of the total dependence symptoms endorsed over the total number of substances used (mean = 2.13 (SD = 1.72)) (24, 29). Exploratory and confirmatory analysis was used to for the remaining measures.
