Population stratification and/or ethnic admixture can be an important source of spurious association in genetic association studies. However, these factors did not affect our GWAS sample and are therefore unlikely to have interfered with our association results. Our study cohort came from an apparently homogenous US mid-west white population, living in Omaha, Nebraska and its surrounding areas. We found that the allele frequencies for the interesting SNPs in our sample are very similar to those reported in the typical and representative Caucasian samples used in the HapMap CEU (Table 2). Furthermore, using the program Structure 2.2 (24), we analyzed our study subjects thoroughly in order to detect potential sub-populations in our sample. In these analyses, all subjects tightly clustered together as a single group, suggesting no significant population substructure in our sample (Appendix III). Furthermore, the measure for population stratification (λ) for our GWAS sample, calculated through the genomic control method (25), was 1.009 for smoking status and 1.012 for cigarette consumption, suggesting essentially no stratification. For the above reasons, the association results, as detected in our GWAS, are not likely to be plagued by spurious associations due to population admixture/stratification.
