Among all substance-use disorders, smoking is the leading cause of preventable death in the United States and is associated with cancer, aerodigestive tract, genitourinary tract, and vascular diseases [8]. Nicotine dependence is most often assessed using measures of cigarette consumption (cigarettes per day, CPD) or dependence (Fagerström Test for Cigarette Dependence, FTCD) [9, 10]. Genetic influences predominate over environmental influences in smoking initiation, but shared environment is important during the adolescent period when the majority of future smokers initiate smoking [11]. Developmental analyses suggest that genetic and environmental factors that influence risk for smoking initiation and consumption are independent in adolescence, but become correlated in emerging adults [12]. Genome-wide meta-analyses of cigarette consumption, dependence, and exposure measures, including linkage [13, 14] and association [15–22] studies, have focused attention on multiple regions, including specific variants in cholinergic, cytochrome oxidase, dopaminergic, and hypoxia response genes.
