For lung cancer, after controlling for categorical CPD and effects of locus 1, we were not able to definitively demonstrate association at either locus 2 or locus 3 after correction for multiple tests. For the mutually adjusted analysis of locus 1 and locus 3 for lung cancer, we observed the same change in the direction for the locus 3 odds ratio that we observed in the joint-SNP analysis of smoking. However, unlike what was seen for smoking, for lung cancer the magnitude (and significance) of the effects did not increase. There are several possible reasons for this, including: chance, the smaller sample size for lung cancer, or qualitative differences in the relationship between these loci and smoking behavior versus the relationship between these loci and lung cancer (after adjusting for smoking quantity). This highlights the challenges posed when attempting to dissect the contributions of multiple loci of modest effect on complex, correlated traits. Further studies, and larger sample sizes, are needed.
