Exact transmission-disequilibrium tests with multiallelic markers.

The transmission-disequilibrium (TD) test is a powerful method for detecting linkage between marker and disease loci in the presence of linkage disequilibrium. For multiallelic markers, we propose the use of exact tests, which are implemented using both an exact algorithm and Markov chain Monte Carlo simulation. Simulation studies show that exact tests improve both the small sample validity and the power of the TD method. We also compared the usual single-affected-offspring sampling scheme to one in which pairs of affected siblings are sampled. Affected-sib-pair sampling greatly increases the power of the TD method and will be most useful when a sample of affected sib pairs is available from prior linkage studies.