A recent genome-wide association study of over 13,000 smokers identified a region on chromosome 15q25.1 associated with smoking intensity (number of cigarettes smoked per day) [44]. This region, spanning the nicotinic acetylcholine receptors, CHRNA5, and CHRNA3, and CHRNB4 and was also identified in a recent GWAS of dichotomized smoking intensity [45], and in two genome-wide association scans of lung cancer [46], [47], It was unclear whether the association between SNPs in this region and lung cancer was due to a genetic effect on smoking behavior, an independent effect on lung carcinogenesis, or both [48]. Two recent candidate gene studies together including almost 5000 smokers both found SNPs in nicotinic receptors including the chr15p25.1 nicotinic receptor loci to be associated with nicotine dependence [49], [50].
