This report describes results of a comprehensive haplotype discovery and nicotine addiction association study within nAChRs genes across three European American populations of 2,827 long-term smokers. Moreover, it tests the a priori hypothesis that associations between nAChR genetic variants and nicotine dependence severity assessed in adulthood will be stronger among smokers who began daily smoking in adolescence than among those who did not. The results show significant dependence-haplotype associations in the CHRNA5-A3-B4 gene cluster occurring only in the early onset subjects, consistent with the hypothesis that the association of genetic risk variants for nicotine addiction may be influenced by the age of onset of daily smoking.
