Recently, genetic findings for nicotine dependence and smoking related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cluster of cholinergic nicotinic receptor subunit genes. The nicotine dependence locus tagged by the single nucleotide polymorphism (SNP) rs16969968 and correlates has been replicated for smoking related traits including cigarettes-per-day and heavy smoking [3]–[11], and has been reported as the most significant association genome-wide in very recent meta-analyses [12]–[14]. This locus has also been associated with risk for lung cancer and COPD in several genome-wide association studies (GWAS) [6], [15]–[18]. This represents an exciting overlap of genetic findings for nicotine dependence and smoking related diseases. Though different SNPs may be reported by each study, the high correlation between the associated SNPs (r2>0.8 with rs16969968) implies that these statistical signals tag the same locus in European-ancestry populations. The SNP rs16969968 results in an amino acid change (D398N) in the alpha5 receptor subunit protein and has been shown to affect receptor function [19].
