The CHRNA5-CHRNA3-CHRNB4 cluster is of further interest because of recent reports of significant association with lung cancer (Amos et al., 2008; Hung et al., 2008; Thorgeirsson et al., 2008), a disease for which cigarette smoking is known to be the major risk factor. The associations with lung cancer were either at the non-synonymous CHRNA5 SNP rs16969968 (p-value 1 × 10−20 (Hung et al., 2008)), or at SNPs highly correlated with it (p = 1.5 × 10−8 at rs1051730 (Thorgeirsson et al., 2008); p = 7× 10−18 at rs1051730 and p = 3× 10−18 at rs8034191 (Amos et al., 2008)). The lung cancer risk allele matches the risk allele for nicotine dependence.
