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Chunk #5 — Subjects and Methods — Linkage scan sample

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Linkage analysis followed by association show NRG1 associated with cannabis dependence in African Americans.
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Subjects were originally ascertained for genetic studies of cocaine dependence (CD) and opioid dependence (OD) using the affected sibling pair (ASP) linkage approach (24, 25). The recruitment procedure has been previously described in detail (26–28). Briefly, there were four recruitment sites: University of Connecticut Health Center, Yale University School of Medicine, Medical University of South Carolina, and McLean Hospital. Families were selected on the basis of having at least two siblings affected with either cocaine and/or opioid dependence. The distribution of family numbers recruited at each site is presented in Supplementary Table 1. Cannabis use played no role in proband selection or pedigree extension. We evaluated these subjects with the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) (29, 30), a polydiagnostic instrument that assesses a range of psychiatric diagnoses, including DSM-IV CaD. Probands with an axis I clinical diagnosis of a major psychotic disorder such as schizophrenia or schizoaffective disorder were excluded from participation. Subjects were classified as AA or EA on the basis of a Bayesian model-based clustering method with ancestry informative genetic markers using STRUCTURE (31, 32), as described previously (28).