Abecasis et al. [2] extended this approach to general pedigrees. In their method, which is implemented in the program QTDT (quantitative transmission disequilibrium test) [3], genotypes are scored as the number of copies of the allele being tested minus 1. That is, an individual with no copies of the tested allele is assigned a -1, an individual with one copy of the allele receives a 0, and an individual with two copies is given a 1. Based on parental genotypes (or sibling genotypes, if parents are untyped), an expected genotype (b) is defined for each non-founder, and deviations (w) from this expectation are used to score allelic transmissions. For founders, b is set to the observed genotype and w is set to 0. As in the sib-pairs analysis described above, the model parameters associated with the between-family and within-family components of the genotype scores, βb and βw, are used to test for population stratification and linkage disequilibrium. Siegmund et al. [4] have proposed a similar method that incorporates an additional within pedigree/between family component for measuring population admixture. In contrast to QTDT, their method is based solely on the trait values for informative non-founders.
