It is well established that genetic factors contribute to risk for tobacco initiation, quantity smoked, nicotine dependence, and smoking persistence [Li et al., 2003; Rhee et al., 2003; Rose et al., 2009; Schnoll et al., 2007]. Neuronal nicotinic acetylcholine receptor (nAChR) subunit genes are among the top candidates for several smoking-related phenotypes because a cluster of nicotinic receptor genes (CHRNA5/CHRNA3/CHRNB4) on chromosome 15q25 has been repeatedly associated with nicotine dependence, smoking behaviors, and lung cancer [Amos et al., 2008; Berrettini et al., 2008; Broms et al., 2012; Furberg et al., 2010; Greenbaum and Lerer, 2009; Hung et al., 2008; Liu et al., 2010; Rose, 2007; Saccone et al., 2010a, 2007; Thorgeirsson et al., 2008; 2010]. This region also contains the nonsynonymous risk variant rs16969968 G/A, that causes a functional amino acid change in the α5 subunit protein (Asp398Asn); the Asparagine (Asn) allele decreases response to a nicotine agonist [Bierut et al., 2008]. The high-risk α5 Asn 398 is associated with reduced Ca2+ permeability and desensitizes faster than the wild type Aspartic acid (Asp) at 398 (α4β2)2 α5 [Kuryatov et al.,
