Work to date suggests that there are significant genetic as well as environmental risk factors for substance dependence disorders (Tsuang et al. 1996, 1998; Kendler & Prescott 1998; Maes et al. 1999; Kendler et al. 2000, 2003, 2007; Miles et al. 2001; Lynskey et al. 2002; Rhee et al. 2003; Wilhelmsen & Ehlers 2005; Ehlers et al. 2007; Hopfer et al. 2007; Agrawal et al. 2008; Kranzler et al. 2008). Multiple genetic and environmental risk factors for substance dependence disorders raise the possibility that a substance dependence diagnosis is a phenotypically similar but etiologically heterogeneous diagnosis. Etiologic heterogeneity also raises the possibility that subtyping of dependence disorders with more homogeneous environmental and genetic determinants might lead to more successful characterization of etiological risk and protective factors.
