The second, and novel, finding from this meta-analysis is the evidence for an additional, distinct, locus in this region that is associated with heavy/light smoking and is genome-wide significant. We demonstrated that locus 3, representing rs588765 and correlates, attains a p-value of p = 6.03×10−9 (OR = 1.17) when we adjust for locus 1 in a logistic regression model. It is notable that the association between locus 3 and CPD is not as apparent in the single-SNP analysis that does not control for locus 1 (e.g. meta-analysis p = 0.0003, OR = 0.93, which does not reach genome-wide significance). The negative correlation between the risk alleles at locus 1 and locus 3 (r = −0.64) masks the effect at the latter locus in single-SNP analysis, a phenomenon known as suppression [31], [32]. The association evidence for both SNPs is strengthened in the joint analysis, with a reversal of the direction of effect for locus 3. This evidence of statistically independent association for locus 3 with smoking in our analysis is compelling given that these SNPs have also been implicated in
