Ancestry was then determined for the proband by using 5239 widely spaced, independent SNPs that had a genotype completion rate of ≥99.9%. The software used was SpectralGEM (48), which estimated five significant dimensions of ancestry (Supplementary Material, Fig. S1). Subsequent clustering on the dimensions of ancestry resulted in six clusters: three clusters of European ancestry, with n = 824, 353 and 87; and three clusters reflecting other major ancestral groups, with n = 68, 54 and 35 (e.g. African and Asian); see also Supplementary Material, Figure S1. The major European cluster (n = 824) was used to determine minor allele frequencies (MAFs), to evaluate Hardy–Weinberg equilibrium (HWE) and Wright's Fst among the genotyping sites. (Note, however, that all three European clusters were used for the ultimate association analyses of this ancestry.) Specific SNPs were eliminated on the basis of the genotypes in this homogeneous European cluster for the following reasons: 5499 were monomorphic; 2102 for completion rate <95%; 132 894 for MAF <0.01; 7734 for HWE P < 0.005; and 89 for Fst > 0.02. Following this QC step, there
