Subjects were recruited at multiple Eastern US sites for genetic studies of drug and alcohol dependence, including genomewide association studies of alcohol,32 cocaine,33 opioid,34 and nicotine dependence.35 The institutional review board at each participating site approved the studies and all subjects provided written informed consent to participate. The National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism issued Certificates of Confidentiality to protect study participants. The sample's demographic details, smoking-related information, and major psychiatric diagnoses are shown in Supplemental Information (Table S2). The subjects were interviewed using the polydiagnostic Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) to obtain DSM-IV diagnoses for all major psychiatric disorders and the additional variables used in the analysis.36 Subjects included in this analysis were current cigarette smokers, i.e., they had smoked within the last week. A smoking-withdrawal symptom score was calculated by summing the reports of DSM-IV smoking withdrawal symptoms. Specifically, subjects were asked about problems that they might have had when they stopped smoking or smoked less tobacco than usual. They answered “yes” or “no” to each of