A simulation study of the effects of assignment of prior identity-by-descent probabilities to unselected sib pairs, in covariance-structure modeling of a quantitative-trait locus

Am J Hum Genet. 1999 Jan;64(1):268-80. doi: 10.1086/302189.

Abstract

Sib pair-selection strategies, designed to identify the most informative sib pairs in order to detect a quantitative-trait locus (QTL), give rise to a missing-data problem in genetic covariance-structure modeling of QTL effects. After selection, phenotypic data are available for all sibs, but marker data-and, consequently, the identity-by-descent (IBD) probabilities-are available only in selected sib pairs. One possible solution to this missing-data problem is to assign prior IBD probabilities (i.e., expected values) to the unselected sib pairs. The effect of this assignment in genetic covariance-structure modeling is investigated in the present paper. Two maximum-likelihood approaches to estimation are considered, the pi-hat approach and the IBD-mixture approach. In the simulations, sample size, selection criteria, QTL-increaser allele frequency, and gene action are manipulated. The results indicate that the assignment of prior IBD probabilities results in serious estimation bias in the pi-hat approach. Bias is also present in the IBD-mixture approach, although here the bias is generally much smaller. The null distribution of the log-likelihood ratio (i.e., in absence of any QTL effect) does not follow the expected null distribution in the pi-hat approach after selection. In the IBD-mixture approach, the null distribution does agree with expectation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Gene Frequency
  • Genetic Markers
  • Humans
  • Models, Genetic*
  • Nuclear Family
  • Quantitative Trait, Heritable*
  • Software

Substances

  • Genetic Markers