Cigarette smoking is a major contributor to cancer, vascular disease and lung disease, and the leading cause of preventable mortality worldwide.1 Nicotine dependence is heritable,2 and genome-wide association study (GWAS) analyses of smoking behaviors and nicotine dependence have unequivocally identified single nucleotide polymorphism (SNP) associations within nicotinic acetylcholine receptor gene clusters on chromosomes 15q25 (CHRNA5-CHRNA3-CHRNB4) and 8p11 (CHRNB3-CHRNA6).3, 4, 5, 6, 7, 8, 9 The largest prior GWAS of smoking behavior was conducted using very large sample sizes (N up to 74 053) and phenotypes such as smoking history (ever vs never), age of onset, smoking cessation (former vs current) and cigarettes per day (CPD).5, 6, 7
