Nicotine dependence was assessed with the Fagerstrom Test of Nicotine Dependence (FTND) because it predicts important dependence attributes such as the likelihood of relapse back to tobacco use and biochemical measures of nicotine self-administration [2],[36],[37]. The FTND assesses a pattern of heavy, compulsive smoking and has been used in other genetic association studies [5]–[9]. Genetic variants were assessed in 2,827 subjects from three European American cohorts with a mean age of 49.6 years (SD = 9.5), 1155 (41%) of whom were females (Table S1). All participants were either current or previous daily cigarette smokers; 222 (8%) had not smoked for at least 2 years prior to participation in the study. One cohort comprised participants in a study of genetic risk factors for nicotine dependence and chronic obstructive pulmonary disease (COPD) recruited in Salt Lake City, Utah (N = 486, UT). Another cohort was made up of participants in randomized trials of smoking cessation interventions recruited in Madison and Milwaukee, Wisconsin (N = 398, WI). A final cohort was drawn from the Lung Health Study (N = 1943, LHS), a multi-site
