We divided the subjects into 2 groups: the “discovery” sample and the “test” sample. The discovery group contained 209 ND cases and 183 controls, all of whom were self-reported European Americans (EAs), whose population assignment was confirmed by the analysis of ancestry-informative markers (AIMs) using STRUCTURE software (30-32). The 209 ND cases were affected siblings recruited from 114 families. Selecting cases with affected family members was expected to increase power, because rare risk variants could co-segregate with disease status, and thus the probability of cases carrying rare risk variants would increase. The majority of the cases (87%) had comorbid cocaine, opioid, or alcohol dependence. The controls were all unrelated and unaffected individuals. The mean age of the cases (53.1% male) was 37.2 (SD = 9.8) years, and of the controls (53.0% male) was 37.6 (SD = 15.0) years.