The (Phase 1) GWAS discovery sample included 5,697 subjects. A second identically ascertained sample comprising 2,549 subjects was used for replication (Phase 3). All of these subjects were recruited for studies of the genetics of drug (opioid or cocaine) or alcohol dependence (AD). The sample consisted of small nuclear families (SNFs) originally collected for linkage studies, and unrelated individuals. Subjects were recruited at five eastern US sites (Table 2). Our previous OD linkage study (7) included a subset of the SNFs included in this study. Subjects gave written informed consent as approved by the institutional review board at each site, and certificates of confidentiality were obtained from NIDA and NIAAA.