Transmission disequilibrium test (TDT) when only one parent is available: The 1-TDT

Abstract

The transmission disequilibrium test (TDT) is a useful method to locate mutations linked to disease genes associated with complex diseases. TDT requires genotypes of affected individuals and their parents. Recently, Ewens and Spielman (Am J Hum Genet 1998;62:450-8) extended the TDT for use in sibships with at least one affected and one unaffected individual and devised a new test called the sib transmission/disequilibrium test (STDT). The S-TDT can be applied to diseases with late age at onset such as non-insulin- dependent diabetes mellitus, psychiatric disorders, and diseases related to aging. For some disorders, it might be relatively easy to obtain the genotype of one parent either because the other parent is not available for study or he/she is not cooperative. Curtis and Sham (Ann Hum Genet 1995;59:323-36) showed that bias in transmitting certain alleles is introduced if only heterozygous parents and homozygous offspring are used in the TDT. In this paper, the authors propose a new test, the 1-TDT, to detect linkage between a candidate locus and a disease locus using genotypes of affected individuals and only one available parent for each affected individual. The test is not biased under the null hypothesis of no linkage or association. The authors validate their test using both simulated and real data sets. Finally, they show how to combine data from different types of families.