Department of Mathematics and Statistics, University of Helsinki, Helsinki FIN-00014, Finland.
Genetics. 2013 Aug;194(4):997-1016. doi: 10.1534/genetics.113.152736. Epub 2013 Jun 14.
In biology, many quantitative traits are dynamic in nature. They can often be described by some smooth functions or curves. A joint analysis of all the repeated measurements of the dynamic traits by functional quantitative trait loci (QTL) mapping methods has the benefits to (1) understand the genetic control of the whole dynamic process of the quantitative traits and (2) improve the statistical power to detect QTL. One crucial issue in functional QTL mapping is how to correctly describe the smoothness of trajectories of functional valued traits. We develop an efficient Bayesian nonparametric multiple-loci procedure for mapping dynamic traits. The method uses the Bayesian P-splines with (nonparametric) B-spline bases to specify the functional form of a QTL trajectory and a random walk prior to automatically determine its degree of smoothness. An efficient deterministic variational Bayes algorithm is used to implement both (1) the search of an optimal subset of QTL among large marker panels and (2) estimation of the genetic effects of the selected QTL changing over time. Our method can be fast even on some large-scale data sets. The advantages of our method are illustrated on both simulated and real data sets.
在生物学中,许多数量性状是动态的。它们通常可以用一些平滑的函数或曲线来描述。通过功能数量性状基因座(QTL)映射方法对所有动态性状的重复测量进行联合分析,具有以下优点:(1)了解数量性状整个动态过程的遗传控制;(2)提高检测 QTL 的统计能力。功能 QTL 映射中的一个关键问题是如何正确描述功能值性状轨迹的平滑度。我们开发了一种用于映射动态性状的高效贝叶斯非参数多基因座方法。该方法使用贝叶斯 P-样条(非参数)B-样条基来指定 QTL 轨迹的函数形式,并使用随机游走先验自动确定其平滑度。使用有效的确定性变分贝叶斯算法来实现(1)在大型标记面板中搜索 QTL 的最佳子集,以及(2)随时间变化估计选定 QTL 的遗传效应。即使在一些大规模数据集上,我们的方法也可以快速运行。我们的方法在模拟和真实数据集上的优势都得到了说明。