In order to account for the effect of population structure on genetic association in these African-American samples, Principal Components Analysis was computed on the GWAS cohorts using all SNPs that passed quality control standards and after exclusion of regions of high linkage disequilibrium and inversions. The first principal component (PC1) explained the largest proportion of genetic variation (22%). In addition, 70 ancestry informative markers were genotyped in 44 Yoruba Nigerians, 39 European Americans as well as the GWAS and replication samples. The African to European ancestral proportion of each sample was estimated using the EM algorithm implemented in the program Frequentist Estimation of individual ancestry proportion (FRAPPE) under a two-population model. PC1 was highly correlated with ancestry informative markers (r = −0.87), suggesting that PC1 largely reflected the ancestry proportions of our GWAS samples. The mean (±s.d.) African ancestry proportions estimated by FRAPPE in cohorts 1–6 were 0.77 ± 0.12, 0.78 ± 0.12, 0.77 ± 0.12, 0.78 ± 0.13, 0.76 ± 0.11, and 0.69 ± 0.14, respectively.
