The likelihood of initiating and persisting in smoking, and ultimately of becoming nicotine dependent, are all influenced by genetic factors, as demonstrated by numerous twin [1–5], linkage [6–9] and candidate gene [10–12] studies. Recently, a whole genome association study by Bierut et al.[13] identified several common variants that appear to be associated with nicotine dependence in Caucasians. In that study, which featured increased single nucleotide polymorphism (SNP) coverage in regions containing potential candidate genes, the most significant associations were for SNPs in genes with functions related to nicotine metabolism and gamma aminobutyric acid (GABAergic) and glutamatergic neurotransmission, showing P-values less than 10−4 for SNPs in, among others, neurexin 1 (NRXN1) and neurexin 3 (NRXN3) as well as the neuronal acetylcholine receptor subunit alpha-5 (CHRNA5) precursor on chromosome 15. A subsequent report by the same group [14] noted that the alpha 5 polymorphism, rs16969968, a non-synonymous coding SNP in exon 4 of CHRNA5, causes an aspartic acid-to-asparagine substitution that alters the function of the nicotine receptor. The findings for the alpha-5 receptor were strengthened by a recent study by Berretini et
