The transmission/disequilibrium test and parental-genotype reconstruction for X-chromosomal markers

Family-based association methods have recently been introduced that allow t esting for linkage in the presence of linkage disequilibrium between a mark er and a disease even if there is only incomplete parental-marker informati on. No such tests are currently available for X-linked markers. This report fills this methodological gap by presenting the X-linked sibling transmiss ion/disequilibrium test (XS-TDT) and the X-linked reconstruction-combinatio n transmission/disequilibrium test (XRC-TDT). As do their autosomal counter parts (S-TDT and RC-TDT), these tests make no assumption about the mode of inheritance of the disease and the ascertainment of the sample. They protec t against spurious association due to population stratification. The two te sts were compared by simulations, which show that (1) the X-linked RC-TDT i s, in general, considerably more powerful than the X-linked S-TDT and (2) t he lack of parental-genotype information can be offset by the typing of a s ufficient number of sibling controls. A freely available SAS implementation of these tests allows the calculation of exact P values.