CHRNA5 and CHRNA3 are nicotinic receptor subunit genes on chromosome 15q25 coding for the α5 nicotinic receptor subunit and the α3 nicotinic receptor subunit, respectively (Fig. 4). The coding sequences are adjacent to one another, and SNPs in the 2 genes are in high linkage disequilibrium (LD). The most biologically compelling association with nicotine dependence was found in rs16969968, a nonsynonymous SNP in the α5 nicotinic receptor subunit gene CHRNA5.30,31 This association has been replicated with either rs16969968 or correlated SNPs in many other independent studies.32–36 rs16969968 is seen in Fig. 4 in the coding region of CHRNA5. rs16969968 is a nonsynonymous SNP for which the minor variant results in an amino acid change of aspartic acid to asparagine. The frequency of the minor allele varies between populations. It ranges from 0% in African populations to 37% in European populations. Although rs16969968 is in the coding sequence of CHRNA5, and a biologically plausible relationship exists between CHRNA5 and nicotine dependence, SNPs in high LD with rs16969968 span a large area encompassing the genes IREB2, PSMA4, CHRNA5, CHRNA3, and CHRNB4. Although
