Examination of LD shows that the r2 between rs9298626 and rs892413 is low, suggesting that these SNPs represent independent association signals (r2 = 0.01; D′ = 0.85). Because the minor allele frequency for rs9298626 is low, the r2 will never be high but the D′ indicates that the minor allele of this SNP is usually but not always on the background of one allele of rs892413. Neither of these SNPs is in significant LD with the previously identified genome-wide significant signal (rs1451240) associated with cigarette consumption and nicotine dependence1423 in this region (r2 = 0.14 between rs9298626 and rs1451240, r2 = 0.35 between rs892413 and rs1451240; Figure 1), although rs9298626 is in high LD (r2 = 0.94) with rs4952, another SNP previously reported to be associated with nicotine dependence18. We find that rs9298626, rs892413 and rs1451240 correspond to different LD bins using r2 = 0.8 as the threshold for defining the bins (Table 1). This is consistent with recent results from our group showing, in an overlapping dataset, that the genome-wide significant signal in this region, tagged by rs1451240, is solely associated with nicotine dependence. Taken together, this suggests that these three SNPs represent different association signals in this region.
