The association between CDH13 and sensitivity to the subjective effects of amphetamine may provide insight into the mechanism by which an allele influences the risk for drug dependence. Drug dependence develops through many stages, including initial experimentation with drugs, continued use, dependence, withdrawal and relapse [74]. Genetic variants might influence risk by impacting one or more of these stages [75]. Whereas a genetic association with the diagnosis of drug dependence provides little insight into which stage is under genetic control, our intermediate phenotype approach suggests that rs3784943 affects magnitude of the initial subjective response to the drug. This would be expected to influence an early stage in the addiction process in which early experimentation with drugs progresses to more frequent drug use. Further studies are needed to assess whether this SNP might also influence the subjective response to other drugs of abuse.
