Results from adoption, twin, and family studies demonstrate a substantial genetic contribution to the risk for CD, including factors both specific to CD and common to different forms of substance dependence [Tsuang et al., 1996, 1998; Kendler and Prescott, 1998; Gelernter et al., 2005a]. The heritability in a female twin population was estimated to be 0.39 for cocaine use and 0.65 for CD symptoms [Kendler and Prescott, 1998]. However, the genetics of CD are complex and there is substantial phenotypic variance in CD populations [Uhl et al., 1995; Gelernter et al., 2005b; Kranzler et al., 2008]. Thus, insights into the genetic etiology of CD are limited by both genetic heterogeneity and the complex clinical manifestations of the disorder [Kranzler et al., 2008; Roncero et al., 2012]. This suggests that the trait defined by the DSM-IV diagnosis of CD [American Psychiatric Association, 1994], which is based on a syndromal model of the disorder, may not be well suited to the identification of specific genetic variants contributing to CD risk.
