association studies (GWAS) using either nicotine dependent smokers as cases and non-dependent smokers as controls [8] or cigarettes per day as a quantitative trait [32] have failed to yield statistically significant findings at the genome-wide level. However, when these studies independently examined nAChR candidate genes [9],[32], evidence was found for associations between common variants in CHRNB3 and the CHRNA5-A3-B4 gene cluster at 15q 24 and their respective phenotypes. Most recently, and subsequent to submission of this article, three separate GWAS reports provide strong evidence for an association between SNP variation at 15q24 and lung cancer [33]–[35]. One study suggests that the effect of 15q24 variants on lung cancer is primarily mediated through smoking behavior [35], while the other studies failed to associate 15q24 variants with smoking behavior and suggest that the disease mechanism with lung cancer is not explained by an association with nicotine addiction [33],[34].
