The neuronal nicotinic acetylcholine receptor genes (nAChRs) are likely candidates for harboring functional variants contributing to nicotine addiction since these ligand-gated ion channels are the initial physiological targets of nicotine in the central and peripheral nervous system. They have also been implicated in nicotine addiction in animals where chronic nicotine exposure leads to persistent changes in brain nAChRs [28],[29], and where engineered mouse models support the crucial role of the α4β2 nAChRs in nicotine addiction [30],[31]. Previous candidate gene association studies using six CHRNA4 SNPs found evidence for associations with measures of nicotine dependence in Chinese men [5], and females of European-American and African-American descent [6]. A wider survey of nAChR gene variants in a case-control study for nicotine dependence found evidence for nominally significant associations in CHRNA7, CHRNA9, CHRNA5 and CHRNB3 in young Israeli women [7]. Several recent genome-wide association studies (GWAS) using either nicotine dependent smokers as cases and non-dependent smokers as controls [8] or cigarettes per day as a quantitative trait [32] have failed to yield statistically significant findings at the genome-wide level. However, when these studies
