Our GWAS discovery sample included 2114 EA and 2602 AA subjects (after exclusion of those not meeting the exposure criterion: 308 AAs and 98 EAs reported never having smoked ≥100 cigarettes). All subjects were recruited for studies of the genetics of drug (opioid or cocaine) or alcohol dependence (1–3). The sample consisted of small nuclear families originally collected for linkage studies (primarily full sibs, half sibs, and parents, generally no more than one parent per family) and unrelated individuals. Subjects (Table S1 in Supplement 1) gave written informed consent as approved by the institutional review board at each site, and certificates of confidentiality were obtained from the National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism. Subjects were administered the Semi-Structured Assessment for Drug Dependence and Alcoholism (15), in which the FTND is embedded. The FTND domains assessed by this instrument are how soon the subject smokes his first cigarette after awakening; whether the subject finds it difficult to refrain from smoking in places where it is forbidden; which cigarette the subject would least like to