Numerous studies have found an association between nicotine dependence and SNPs in the α5 nicotinic receptor gene, CHRNA5(5–12).To maximize the power to detect genetic variants associated with smoking quantity (as an alternative to nicotine dependence), three large research consortia performed genome-wide association meta-analyses of cigarettes per day (CPD)in a combined sample of over 75,000 subjects (13–15).The strongest association was the variant in CHRNA5, with a combined p-value less than 1 × 10−70. However, several other variants were discovered with genome-wide significance: variants near the nicotinic receptor subunit genes CHRNB3 and CHRNA6 on chromosome 8 (rs6474412, p=1.4 × 10−8,a region previously associated with other nicotine phenotypes(16–20)),variants near the nicotine metabolizing enzyme genes CYP2A6 and CYP2B6 on chromosome 19(rs4105144, p=2.2 × 10−12), and variants in a non-coding region located on chromosome 10q23(rs1329650, p=5.7 × 10−10).
