Recently, three independent genome-wide association studies (GWAS) provided strong evidence for associations between the variants of the CHRNA5/A3/B4 cluster and lung cancer (Amos and others 2008; Hung and others 2008; Liu and others 2008; McKay and others 2008; Thorgeirsson and others 2008; Wang and others 2008). Regarding the association of this gene cluster with ND, the results are less clear. One study (Thorgeirsson and others 2008) revealed a significant association of rs1051730 within CHRNA3 with smoking quantity (P = 5.0 × 10−16) in approximately 11,000 Icelandic smokers, whereas another study (Amos and others 2008) reported weak evidence of an association of SNPs rs1051730 and rs8034191 with smoking behavior in former but not current smokers. The third study (Hung and others 2008) found no association of SNPs 8034191 and rs16969968 with smoking dependence. Several other studies provide additional independent evidence pertaining to the association of variants of this gene cluster with ND. For example, Saccone et al. (2007) first reported significant associations of CHRNA5/A3/B4 cluster variants with ND in a large-scale candidate gene-based case-control study of 1050 cases and 879 controls
