The three GWS SNPs on chromosome 8p11 in samples of African and European ancestries—rs13280604, rs6474412, and rs1451240—are in perfect LD with each other18, 25 and also with a variant (rs13277254) suggestively associated with the ND status of smokers in the first ND GWAS.92 As noted by Rice et al.,25 although the dichotomized FTND appeared to have an equivalent relation with rs1451240 across ethnicities, the relation between this SNP and CPD was much weaker in AAs than in EAs. The other two SNPs were both significantly associated with CPD in Europeans.18 These associated SNPs are either intergenic or intronic, which may tag causal variation(s) within the LD block that contains CHRNB3 and CHRNA6 or regulate the expression of the two genes directly. Significant association of variants in CHRNB3 and CHRNA6 with ND was confirmed in eight candidate gene association studies with diverse population ancestries and smoking traits (Table 2).21-24, 106, 127-129 Cui et al.21 obtained a close to GWS meta-p value for an upstream variant of CHRNB3 (rs4736835) in a candidate gene association study of 22,654 subjects with African, European, and East Asian ancestries.
