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This article is part of the supplement: Genetic Analysis Workshop 13: Analysis of Longitudinal Family Data for Complex Diseases and Related Risk Factors

Open Access Proceedings

On different approximations to multilocus identity-by-descent calculations and the resulting power of variance component-based linkage analysis

Harald HH Göring*, Jeff T Williams, Thomas D Dyer and John Blangero

Author Affiliations

Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas, USA

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BMC Genetics 2003, 4(Suppl 1):S72  doi:10.1186/1471-2156-4-S1-S72

Published: 31 December 2003

Abstract

An empirical comparison between three different methods for estimation of pair-wise identity-by-descent (IBD) sharing at marker loci was conducted in order to quantify the resulting differences in power and localization precision in variance components-based linkage analysis. On the examined simulated, error-free data set, it was found that an increase in accuracy of allele sharing calculation resulted in an increase in power to detect linkage. Linkage analysis based on approximate multi-marker IBD matrices computed by a Markov chain Monte Carlo approach was much more powerful than linkage analysis based on exact single-marker IBD probabilities. A "multiple two-point" approximation to true "multipoint" IBD computation was found to be roughly intermediate in power. Both multi-marker approaches were similar to each other in accuracy of localization of the quantitative trait locus and far superior to the single-marker approach. The overall conclusions of this study with respect to power are expected to also hold for different data structures and situations, even though the degree of superiority of one approach over another depends on the specific circumstances. It should be kept in mind, however, that an increase in computational accuracy is expected to go hand in hand with a decrease in robustness to various sources of errors.