The transmission/disequilibrium test (TDT), which detects linkage between a marker and disease loci in the presence of linkage disequilibrium, was introduced by Spielman et al. The original TDT requires families in which the genotypes ate known for both parents and for at least one affected offspring, and this limits its applicability to diseases with late onset. The sib-TDT, or S-TDT which utilizes families with affected and unaffected siblings, was introduced as an alternative method, by Spielman and Ewens, and the TDT and S-TDT can be combined in an overall test (i.e., a combined-TDT, or C-TDT). The TDT statistics described so far are for autosomal chromosomes. We have extended these TDT methods to test for linkage between S-linked markers and diseases that affect either males only or both sexes. For diseases of late onset, when parental genotypes are often unavailable, the X-linkage C-TDT may allow for more power than is provided by the X-linknge TDT alone.
