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

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 co... Mehr ...

Verfasser: Dolan, C.
Boomsma, D.I.
Neale, M.C.
Dokumenttyp: Artikel
Erscheinungsdatum: 1999
Reihe/Periodikum: Dolan , C , Boomsma , D I & Neale , M C 1999 , ' 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 ' , American Journal of Human Genetics , vol. 64 , no. 1 , pp. 268-280 . https://doi.org/10.1086/302189
Schlagwörter: /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_ / name=Netherlands Twin Register (NTR)
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29211792
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://research.vu.nl/en/publications/6deab57f-40ad-41e7-b97c-e203adf64c40

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.