with known SNPs related to nicotine dependence in this region. In EUR, 13 SNPs in this LD bin, including the tag SNP rs1451240, have extreme iHS values. All have positive values, indicating the presence of unusually long haplotypes containing the ancestral allele suggesting that the ancestral allele, which is associated with a greater risk of nicotine dependence is being favored by selection. An LD bin in the CHRNB3-A6 region bin that has been shown to have SNPs significantly associated with increased risk for cocaine dependence [17] also contained an abundance of SNPs with extreme iHS values (S1 Table). This bin is fairly large and spans the entire CHRNB3-A6 cluster. It contains rs4952 and rs4953, two low frequency synonymous variants in CHRNB3 that have previously been reported to be associated with lower risk for nicotine dependence [10]. All SNPs in the bin are present at around 10% in AFR and 4% in EUR but absent in ASN, possibly explaining the lack of extreme iHS values in the ASN population. Overall, 40% of the SNPs in this bin showed extreme values in AFR and 15% of the SNPs in this bin showed extreme values in EUR. As these SNPs are absent from
