CD is highly comorbid with other SD (Kranzler et al 2008). In our family sample, the majority of CD cases were comorbid with another SD, including 77.0% with nicotine dependence (ND), 64.2% with opioid dependence (OD), 52.1% with alcohol dependence (AD), 35.9% with marijuana dependence (MD) and 26.0% with other types of SD (R-SD). Because of the high degree of comorbidity, it was not feasible to study a “CD-only” phenotype (4%, n=22) (nor is this phenotype important clinically, compared to comorbid phenotypes). Consequently, we excluded different types of comorbid SD one-by-one to control for the potential confounding effects from other SD (Figure 3). This one-by-one exclusion created five subgroups of CD, i.e. CDnoAD (CD without comorbid AD), CDnoOD (CD without comorbid OD) CDnoMD (CD without comorbid MD), CDnoND (CD without comorbid ND) and CDnoR-SD (CD without comorbid R-SD). After excluding the effects of AD, OD, MD and R-SD, the association signal remained significant for SNP8 (PCDnoAD=0.012; PCDnoOD=0.021; PCDnoMD=0.014; PCDnoR-SD=0.020). After excluding ND, the association signal for CDnoND decreased; a “trend-level possible” association signal remained (P=0.071). At SNP3, the “trend-level possible”
