we subdivided the 144 smokers into high (n = 72) and low-dependent (n = 72) categories. Even with this small selected sample set, a nominally significant association signal (P<0.01) was observed for five SNPs located in the CHRNA5-A3-B4 cluster on chromosome 15q25: rs951266 (intronic A5), rs16969968 (nonsynonymous A5), rs8192482 (3′-UTR A5), rs4887067 (intergenic A5-A3) and rs17487223 (intronic B4). All five SNPs are in strong linkage disequilibrium. In order to extend this survey, we defined haplotype structures in all nAChR subunits based on inference from the unphased resequencing data, and derived a minimal set of tagging SNPs (n = 87) for genotyping in the larger three-cohort sample.