We next measured Tajima’s D in the CHRNA5-A3-B4 gene cluster on chromosome 15. In this region, we analyzed a 120 kb region that includes the nicotinic receptor gene cluster as well as ~18 kb upstream of CHRNA5. This was done to ensure that we included the large region upstream of CHRNA5 that has been associated with regulation of the level of mRNA expression for CHRNA5 [28]. Fig 1B shows the distribution of Tajima’s D values in the sliding windows in the CHRNA5-A3-B4 region in AFR, ASN and EUR. Overall, we observed increased numbers of sliding windows with extreme Tajima’s D values in each of the three populations, which is not consistent with a neutral evolution and demography in this region (Table 1). Of note, several SNPs previously shown to be associated with nicotine, alcohol and/or cocaine dependence [7,10–14] are within regions with high Tajima’s D values. Additionally, within the EUR population, these regions also harbor SNPs in an LD bin tagged by rs5887655 previously shown to be significantly associated with CHRNA5 mRNA expression in the brain [28]. Table 2 summarizes the Tajima’s D values for windows containing associated SNPs in each of these two LD bins.
