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用于有序性状的全基因组相互作用数量性状位点的贝叶斯定位

Bayesian mapping of genomewide interacting quantitative trait loci for ordinal traits.

作者信息

Yi Nengjun, Banerjee Samprit, Pomp Daniel, Yandell Brian S

机构信息

Section on Statistical Genetics, Department of Biostatistics, University of Alabama, Birmingham, Alabama 35294-0022, USA.

出版信息

Genetics. 2007 Jul;176(3):1855-64. doi: 10.1534/genetics.107.071142. Epub 2007 May 16.

Abstract

Development of statistical methods and software for mapping interacting QTL has been the focus of much recent research. We previously developed a Bayesian model selection framework, based on the composite model space approach, for mapping multiple epistatic QTL affecting continuous traits. In this study we extend the composite model space approach to complex ordinal traits in experimental crosses. We jointly model main and epistatic effects of QTL and environmental factors on the basis of the ordinal probit model (also called threshold model) that assumes a latent continuous trait underlies the generation of the ordinal phenotypes through a set of unknown thresholds. A data augmentation approach is developed to jointly generate the latent data and the thresholds. The proposed ordinal probit model, combined with the composite model space framework for continuous traits, offers a convenient way for genomewide interacting QTL analysis of ordinal traits. We illustrate the proposed method by detecting new QTL and epistatic effects for an ordinal trait, dead fetuses, in a F(2) intercross of mice. Utility and flexibility of the method are also demonstrated using a simulated data set. Our method has been implemented in the freely available package R/qtlbim, which greatly facilitates the general usage of the Bayesian methodology for genomewide interacting QTL analysis for continuous, binary, and ordinal traits in experimental crosses.

摘要

统计方法和软件的开发用于定位相互作用的数量性状基因座一直是近期众多研究的焦点。我们之前基于复合模型空间方法开发了一个贝叶斯模型选择框架,用于定位影响连续性状的多个上位性数量性状基因座。在本研究中,我们将复合模型空间方法扩展到实验杂交中的复杂有序性状。我们基于有序概率单位模型(也称为阈值模型)联合建模数量性状基因座和环境因素的主效应及上位效应,该模型假设一个潜在的连续性状通过一组未知阈值构成有序表型的产生基础。我们开发了一种数据增强方法来联合生成潜在数据和阈值。所提出的有序概率单位模型与用于连续性状的复合模型空间框架相结合,为有序性状的全基因组相互作用数量性状基因座分析提供了一种便捷方式。我们通过在小鼠的F(2)杂交中检测一个有序性状(死胎)的新数量性状基因座和上位效应来说明所提出的方法。使用一个模拟数据集也证明了该方法的实用性和灵活性。我们的方法已在免费可用的软件包R/qtlbim中实现,可以极大地促进贝叶斯方法在实验杂交中对连续、二元和有序性状进行全基因组相互作用数量性状基因座分析的广泛应用。

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