Some unrelated controls will not be similar enough to any probands to merit inclusion in the study. For example, the HapMap trios can only be successfully matched to a subset of the full European sample in POPRES (Figure 1). Likewise some unrelated cases might not be well matched by any unrelated controls in the study. SpectralGEM provides features that facilitate the removal of individuals who cannot be successfully matched because their genetic ancestry is too remote, relative to the others in the sample [12, 17]. These individuals should be removed from further consideration in the association study. Once the strata are established, a natural next step is to compare the differences in genotypes between the case and controls by using CLR.
