The Applicability of Combination Methods for Combining the Transmission / Disequilibrium Test and the Mean test using Affected Sib Pairs

Abstract

The transmission/disequilibrium test (TDT) and the mean test are the two major nonparametric methods used in linkage analysis. Using case-parent triad data the TDT method tests the equality of the probabilities of a marker allele transmitted or not transmitted with the disease gene of a heterozygous parent. On the other hand, the mean test tests the goodness-of-fit of the observed and expected distributions of the number of alleles shared identical by descent using affected sib-pair data. It has been clarified in the literature that the mean test has higher power than the TDT when linkage disequilibrium (LD) is weak but the TDT has higher power than the mean test when LD is strong. These results indicate that both tests are sensitive to linkage disequilibrium, though their responses are different. In this talk, I will discuss several available combining methods for the development of a robust method against the interference of linkage disequilibrium. Numerical comparisons are presented to evaluate their performance with the TDT, the mean test, the combining procedures proposed by Spielman et al. [1993] and Huang and Jiang [1999].