In contrast, the remaining significant SNP in the CHRNA5-CHRNA3-CHRNB4 cluster, rs578776, is not correlated with rs16969968 or its bin. The LD between rs578776 and rs16969968 is r2 = 0.20 overall (0.196 in cases, 0.205 in controls) with D’ = −1.0, due to the LD being in repulsion phase. We thus observed two distinct loci in the CHRNA5-CHRNA3-CHRNB4 gene cluster whose significant association with nicotine dependence is not simply explained by LD between these loci. Table II, column 7 clarifies that for rs16969968 the “risk” allele (meaning the allele more common in cases than in controls) is the minor allele, while for rs578776 the risk allele is the major allele. Thus, recoding the genotypes with the major allele as the reference allele would give an odds ratio of 1.31 for rs16969968 versus a “protective” odds ratio of 0.75 for rs578776.
