Gene variants in CHRNA5-A3-B4, particularly rs16969968 and correlated SNPs, have been consistently associated with heaviness of smoking and the levels of nicotine dependence in Caucasians (9-11, 25). In contrast to a recent meta-analysis in African American smokers (21), in the current study we did not observe any significant association between CHRNA5-A3-B4 variants, particularly rs2036527, and baseline smoking behaviors, including self-reported CPD, plasma cotinine levels or urinary total nicotine equivalents. This was unexpected since our study, although smaller in size compared to the meta-analysis, had objective biomarker data. Since it is well known that self-reported CPD does not account for the depth of inhalation and is a relatively weak marker of tobacco exposure (26), we expected the accuracy of biomarker data to compensate for the smaller sample size (N=1142). One reason for the lack of association between tobacco exposure and rs2036527 in our study may be that the previous meta-analyses included a substantial number of former smokers whereas our studies included only current smokers (21). It was previously observed that the influence of CHRNA5-A3-B4 gene variants on self-reported CPD is stronger
