Varona L, García-Cortés L A, Pérez-Enciso M
Area de Producció Animal, Centre UdL-IRTA, c/ Rovira Roure 177, 25198 Lleida, Spain.
Genet Sel Evol. 2001 Mar-Apr;33(2):133-52. doi: 10.1186/1297-9686-33-2-133.
A fundamental issue in quantitative trait locus (QTL) mapping is to determine the plausibility of the presence of a QTL at a given genome location. Bayesian analysis offers an attractive way of testing alternative models (here, QTL vs. no-QTL) via the Bayes factor. There have been several numerical approaches to computing the Bayes factor, mostly based on Markov Chain Monte Carlo (MCMC), but these strategies are subject to numerical or stability problems. We propose a simple and stable approach to calculating the Bayes factor between nested models. The procedure is based on a reparameterization of a variance component model in terms of intra-class correlation. The Bayes factor can then be easily calculated from the output of a MCMC scheme by averaging conditional densities at the null intra-class correlation. We studied the performance of the method using simulation. We applied this approach to QTL analysis in an outbred population. We also compared it with the Likelihood Ratio Test and we analyzed its stability. Simulation results were very similar to the simulated parameters. The posterior probability of the QTL model increases as the QTL effect does. The location of the QTL was also correctly obtained. The use of meta-analysis is suggested from the properties of the Bayes factor.
数量性状基因座(QTL)定位中的一个基本问题是确定给定基因组位置存在QTL的合理性。贝叶斯分析提供了一种通过贝叶斯因子检验替代模型(此处为QTL模型与无QTL模型)的有吸引力的方法。已经有几种计算贝叶斯因子的数值方法,大多基于马尔可夫链蒙特卡罗(MCMC),但这些策略存在数值或稳定性问题。我们提出了一种简单且稳定的方法来计算嵌套模型之间的贝叶斯因子。该过程基于根据组内相关对方差分量模型进行重新参数化。然后,通过对零组内相关时的条件密度求平均,可以轻松地从MCMC方案的输出中计算出贝叶斯因子。我们通过模拟研究了该方法的性能。我们将此方法应用于远交群体的QTL分析。我们还将其与似然比检验进行了比较,并分析了其稳定性。模拟结果与模拟参数非常相似。QTL模型的后验概率随着QTL效应的增加而增加。QTL的位置也被正确获得。根据贝叶斯因子的性质,建议使用荟萃分析。