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Exact transmission-disequilibrium tests with multiallelic markers
M A Cleves1, J M Olson, K B Jacobs
1Department of Epidemiology and Biostatistics, Rammelkamp Center for Education and Research, Case Western Reserve University, Cleveland, Ohio, USA.
Genetic Epidemiology
|January 1, 1997
Summary
Exact tests enhance the transmission-disequilibrium (TD) test for genetic linkage analysis with multiallelic markers. Sampling affected sibling pairs significantly boosts the TD test's power, especially in genetic studies.
Area of Science:
- Statistical Genetics
- Genetic Epidemiology
- Bioinformatics
Background:
- The transmission-disequilibrium (TD) test is a key method for identifying genetic linkage between markers and disease loci.
- Linkage disequilibrium presents challenges for traditional TD test applications, particularly with multiallelic markers.
Purpose of the Study:
- To develop and evaluate exact tests for the TD method with multiallelic markers.
- To compare the efficacy of different sampling strategies, including affected-offspring and affected-sibling pairs.
Main Methods:
- Implementation of exact tests using an exact algorithm and Markov chain Monte Carlo (MCMC) simulation.
- Comparison of single-affected-offspring sampling with affected-sibling-pair sampling schemes.
Main Results:
- Exact tests demonstrate improved small sample validity and statistical power for the TD method.
- Affected-sibling-pair sampling substantially increases the power of the TD test compared to single-offspring sampling.
Conclusions:
- Exact tests offer a robust approach for TD analysis with multiallelic markers.
- Affected-sibling-pair sampling is a highly effective strategy for enhancing genetic linkage detection power in TD studies.