The GWAS discovery sample included a total of 5,697 subjects. A replication dataset (identically evaluated) was comprised of 2,549 subjects and was genotyped for individual markers. (Public domain GWASed samples were included in some analyses as well, as described below.) All subjects were recruited for studies of the genetics of cocaine, opioid, or alcohol dependence. The sample consisted of small nuclear families (SNFs) originally collected for linkage studies, and unrelated individuals. Subjects were recruited at five US clinical sites: Yale University School of Medicine (APT Foundation; New Haven, CT), the University of Connecticut Health Center (Farmington, CT), the University of Pennsylvania Perelman School of Medicine (Philadelphia, PA), the Medical University of South Carolina (Charleston, SC), and McLean Hospital (Belmont, MA). Details regarding the sample can be found in Table 1 and Supplementary Tables 1 and 2. Our previous CD linkage study5 included a subset of the SNFs included in this study.