In summary, we have demonstrated that there are two groups of SNPs with low correlation to each other in the CHRNA5-CHRNA3-CHRNB4 gene cluster that are associated with heavy smoking with a very high degree of statistical significance. Individuals who have the risk genotype without the protective genotype have over twice the odds of heavy smoking compared to individuals with the opposite genotype combination. These findings strongly argue for further study of the α5 AChR subunit in nicotine dependence-related phenotypes in humans to gain insight into the molecular basis of smoking behavior that confer a high risk of lung cancer and other diseases.
