Several SNPs in the CHRNB3-A6 locus on chromosome 8 have previously been associated with a decreased risk of nicotine dependence [18]. One of these, rs1451240, was present in a window that showed extreme values in both the Tajima’s D test and iHS. The extreme positive iHS value in the window including rs1451240 indicates that the haplotype containing the ancestral allele is being positively selected. As the derived allele provides protection from nicotine addiction, this suggests that it is the allele that is associated with a greater risk of nicotine dependence that is being selected. Since highly concentrated sources of nicotine were not present in the ancestral environment, it seems likely that this phenotype of nicotine dependence would have hitchhiked along with a more beneficial phenotype. One challenge with this region is that it is approximately 1,500,000 bp away from the centromere of chromosome 8. This could be affecting the results by some unknown mechanism. However, the region including the nicotinic receptors on chromosome 8 was among the top 5% of iHS scores among all regions tested in the genome.
