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应用于全基因组关联研究的贝叶斯方法。

Bayesian methods applied to GWAS.

作者信息

Fernando Rohan L, Garrick Dorian

机构信息

Department of Animal Science, Iowa State University, Ames, IA, USA.

出版信息

Methods Mol Biol. 2013;1019:237-74. doi: 10.1007/978-1-62703-447-0_10.

Abstract

Bayesian multiple-regression methods are being successfully used for genomic prediction and selection. These regression models simultaneously fit many more markers than the number of observations available for the analysis. Thus, the Bayes theorem is used to combine prior beliefs of marker effects, which are expressed in terms of prior distributions, with information from data for inference. Often, the analyses are too complex for closed-form solutions and Markov chain Monte Carlo (MCMC) sampling is used to draw inferences from posterior distributions. This chapter describes how these Bayesian multiple-regression analyses can be used for GWAS. In most GWAS, false positives are controlled by limiting the genome-wise error rate, which is the probability of one or more false-positive results, to a small value. As the number of test in GWAS is very large, this results in very low power. Here we show how in Bayesian GWAS false positives can be controlled by limiting the proportion of false-positive results among all positives to some small value. The advantage of this approach is that the power of detecting associations is not inversely related to the number of markers.

摘要

贝叶斯多元回归方法正成功应用于基因组预测和选择。这些回归模型同时拟合的标记数量远多于可用于分析的观测值数量。因此,贝叶斯定理用于结合标记效应的先验信念(以先验分布表示)与来自数据的信息进行推断。通常,分析过于复杂,无法得出封闭形式的解,因此使用马尔可夫链蒙特卡罗(MCMC)采样从后验分布中进行推断。本章描述了如何将这些贝叶斯多元回归分析用于全基因组关联研究(GWAS)。在大多数GWAS中,通过将全基因组错误率(即一个或多个假阳性结果的概率)限制在一个较小的值来控制假阳性。由于GWAS中的测试数量非常大,这导致检测力非常低。在这里,我们展示了在贝叶斯GWAS中如何通过将所有阳性结果中假阳性结果的比例限制在某个较小的值来控制假阳性。这种方法的优点是检测关联的能力与标记数量没有反比关系。

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