Third, in this study, we not only performed association analyses of this region with the three major smoking-related phenotypes at the SNP and haplotype levels, as in most reported association studies of the region with smoking, but also performed extensive gene-gene interaction analysis exclusively in this region. This is important in that: (1) all nAChR subunits except alpha 7 must assemble under appropriate compositions in order to form functional receptors; and (2) it is still undetermined whether other uncharacterized genes of this region contribute to smoking-related phenotypes [12]. Our gene-gene interaction results in the male sample indicate clearly that some variants exist within the region between rs7163730 in LOC123688 and rs11072793 in the intergenic region downstream from the 5′ end of CHRNB4 that are contributing to SI through gene-gene interactions. This appears consistent with findings from our recent study showing an association of the region with ND in European American and African American samples [18]. This has been the case for several other genes also. For example, we recently detected a significant interaction between variants of CHRNA4 and CHRNB2 in
