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

被引:20
作者
Dolan, CV
Boomsma, DI
Neale, MC
机构
[1] Univ Amsterdam, Fac Psychol, NL-1018 WB Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Dept Psychol, Amsterdam, Netherlands
[3] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA
关键词
D O I
10.1086/302189
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 LED-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 LED-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 LED-mixture approach, the null distribution does agree with expectation.
引用
收藏
页码:268 / 280
页数:13
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