As another limitation of our study, we did not adjust for multiple testing (for testing multiple smoking behavior-related phenotypes in our GWAS and the AA replication cohorts). However, due to the limited number of different phenotypes (i.e., 2 phenotypes in the GWAS cohort and 3 phenotypes in the AA cohort) and the fact that these phenotypes are correlated smoking behavior traits, adjusting for multiple testing may only have minor effects on the current results. Even with the most stringent correction, Bonferroni correction that does not consider correlation of the multiple traits, the most significant SNP in our GWAS, rs4956302, is still significant at the corrected genome-wide significance level of 2.1×10−7 (= 4.2×10−7/2) for association with smoking status, and the most significant SNP in our AA replication study, rs17354547, is also significant at the corrected significance level of 0.017 (=0.05/3) for association with HSI. Again, replication of our GWAS findings in two different cohorts attests to the findings' robustness and may have attenuated the potential problem due to multiple testing of several phenotypes.
