Prior linkage studies have identified genomic susceptibility regions for single SD diagnoses [Gelernter et al., 2004, 2005, 2006a, 2007; Han et al., 2010; Panhuysen et al., 2010]. In this study, we proceed from the well-supported hypothesis that substance dependence traits share common genetic liability to some varying extent. Given the potential for shared genetic liability, investigation of dependence on multiple substances makes it possible to gain substantial phenotypic information and statistical power to map-shared susceptibility regions. In this autosomal linkage scan, we used dependence on three illicit drugs (cannabis, cocaine, and opioid) and two legal substances (alcohol and nicotine) as a phenotype. We used fuzzy clustering analysis [Kaufman and Rousseeuw, 1990] to reduce the dimensions and derive a more homogeneous quantitative trait to identify a genetic component common to multiple SDs. Fuzzy clustering yields a membership coefficient that contains more information than the standard hard clustering approaches.
