Nicotinic acetylcholine receptors (nAChRs) are highly expressed in the central nerve system and their binding to nicotine, the most active pharmacological compound in cigarettes, triggers the physiological and pharmacological responses to tobacco smoking. Animal model studies have shown that these nAChRs are critical to tolerance, reward and the modulation of mesolimbic dopamine function that are essential to the development of nicotine dependence [Mineur and Picciotto, [2008]]. Many genes in the human genome encode for the nicotinic receptors and several genes have been studied in smoking and nicotine dependence in human subjects [Silverman et al., [2000]; Feng et al., [2004]; Li et al., [2005]; Saccone et al., [2007]; Winterer et al., [2007]]. In a recent study, Saccone et al. reported associations in multiple single nucleotide polymorphisms (SNPs) in CHRNA5, CHRNA3, and CHRNB4 gene cluster on 15q25. However, due to the large number of markers tested, the significance of these results did not survive correction for multiple testing. More recently, several other studies provided independent evidence that the CHRNA5, CHRNA3, and CHRNB4 locus is associated with heavy smoking and nicotine dependence [Berrettini
