Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Genetics. 2010 Mar;184(3):839-52. doi: 10.1534/genetics.109.113183. Epub 2010 Jan 4.
We describe a fast hierarchical Bayesian method for mapping quantitative trait loci by haplotype-based association, applicable when haplotypes are not observed directly but are inferred from multiple marker genotypes. The method avoids the use of a Monte Carlo Markov chain by employing priors for which the likelihood factorizes completely. It is parameterized by a single hyperparameter, the fraction of variance explained by the quantitative trait locus, compared to the frequentist fixed-effects model, which requires a parameter for the phenotypic effect of each combination of haplotypes; nevertheless it still provides estimates of haplotype effects. We use simulation to show that the method matches the power of the frequentist regression model and, when the haplotypes are inferred, exceeds it for small QTL effect sizes. The Bayesian estimates of the haplotype effects are more accurate than the frequentist estimates, for both known and inferred haplotypes, which indicates that this advantage is independent of the effect of uncertainty in haplotype inference and will hold in comparison with frequentist methods in general. We apply the method to data from a panel of recombinant inbred lines of Arabidopsis thaliana, descended from 19 inbred founders.
我们描述了一种快速的基于层次贝叶斯方法的基于单倍型的数量性状位点作图方法,适用于单倍型不是直接观察到,而是从多个标记基因型推断出来的情况。该方法通过使用完全因式分解似然的先验来避免使用蒙特卡罗马尔可夫链。它由一个单一的超参数参数化,与需要每个单倍型组合表型效应参数的频率固定效应模型相比,该模型由数量性状位点解释的方差分数来表示;尽管如此,它仍然提供了单倍型效应的估计。我们通过模拟表明,该方法与频率回归模型的功效相匹配,并且当推断单倍型时,对于小的 QTL 效应大小,它的功效超过了后者。贝叶斯对单倍型效应的估计比频率估计更准确,无论是已知的还是推断的单倍型,这表明这种优势独立于单倍型推断不确定性的影响,并将与一般的频率方法进行比较。我们将该方法应用于来自拟南芥 19 个自交系的重组近交系系谱的面板数据中。