A variety of TDT-like tests have been suggested starting with Rubinstein et al [19]. Curtis and Sham studied a multi-allelic TDT with incorporation of missing parents [20], [21]. This was extended by Spielman et al and Horvath et al [22], [23] with the TDT applied to different family structures in their sib-ship tests. For an allele of interest at a marker locus, the sib-ship test essentially compares the frequency of that allele among affected individuals with the frequency of the allele among unaffected individuals, which allows the TDT to be applied to diseases with late age of onset, such as non-insulin-dependent diabetes, cardiovascular diseases, Alzheimer’s disease, and other diseases related to aging. Several studies also discussed the application of the TDT for mapping quantitative trait loci [24]–[30]. Gordon et al.’s TDTae allows for genotyping errors in the analysis and accommodates various error models [31]. As discussed above, multiple affected and unaffected siblings are often collected and used for both linkage and association analysis. The family-based association test (FBAT) generalized the TDT model on various phenotypic traits and multiple markers [32]–[36].
