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

BMC Genet. 2003 Dec 31;4 Suppl 1(Suppl 1):S72. doi: 10.1186/1471-2156-4-S1-S72.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Body Height / genetics
  • Chromosome Mapping / statistics & numerical data
  • Chromosomes, Human, Pair 5 / genetics
  • Cohort Studies
  • Empirical Research
  • Female
  • Genetic Linkage / genetics*
  • Genetic Markers / genetics
  • Humans
  • Male
  • Markov Chains
  • Models, Genetic
  • Monte Carlo Method
  • Quantitative Trait Loci / genetics

Substances

  • Genetic Markers