To develop successful prevention and intervention techniques, it is important to understand the etiology of substance dependence and identify those at most risk. Numerous studies have demonstrated that, regardless of the substance of interest, both genetic predisposition and environmental influences contribute to the development of substance dependence in adolescents (Button et al., 2007b; Dick and Bierut, 2006; Heath et al., 1997; Rhee et al., 2003; Tsuang et al., 1996). Using a subsample of the participants described for the current study, we previously demonstrated that the heritability for a generalized vulnerability to develop dependence on drugs (dependence vulnerability; DV) is 0.40 (Button et al., 2006). However, recent research has demonstrated that the extent to which genes affect both substance use and associated problems may be moderated by exposure to different environments. For example, urbanicity (Dick et al., 2001; Rose et al., 2001) and marital status (Dick et al., 2006) have both been found to affect the heritability of alcoholism, with higher heritability for alcohol use in urban (versus rural) communities and unmarried women. Therefore, previously reported heritabilities for substance use, abuse,