The CHRNA5 subunit has been implicated as a potential risk factor for nicotine dependence [13] resulting from an amino acid variant in a highly conserved region of the intracellular domain [14]. The present results substantiated these observations and extended the findings for dependent and non-dependent smokers in the Bierut et al. study [13] to nicotine-dependent regular smokers versus never-smokers. A recent report by Berretinini et al.[15] of association between a CHRNA5/CHRNA3 gene cluster and number of cigarettes smoked per day—a different smoking phenotype—provides further support for the influence of the alpha-5 subunit on smoking across different contrasts. Specifically, in the Bierut et al. study, controls were current smokers with FTND scores of zero; in the Berretinini et al. study, controls were individuals (both current smokers and never-smokers) consuming fewer than five cigarettes per day; in the present study, controls were never-smokers who had tried at least one cigarette but had subsequently smoked fewer than 100 cigarettes in their life-time.
