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

C. Dolan, D.I. Boomsma, M.C. Neale

Research output: Contribution to JournalArticleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)268-280
Number of pages13
JournalAmerican Journal of Human Genetics
Volume64
Issue number1
DOIs
Publication statusPublished - 1999

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