from transmitted and un-transmitted alleles) (49). Unrelated SAGE controls were matched by genetic ancestry to probands and combined with the ‘pseudo-controls’ produced by the family-based analysis: first, by spectral analysis, we estimated the genetic ancestry of probands and unrelated controls (48); then, using the optimal matching algorithm, we formed genetically homogeneous strata (52), each consisting of a single proband and one or more unrelated controls. In those strata where a single control was matched with more than one proband, the control was paired with the best match in the stratum and the remaining probands each form their own stratum. Finally, within each stratum, we contrasted the genotype of the proband with the genotypes of the matched controls and pseudo-controls via conditional logistic regression.
