Basu Saonli, Pankow James S
Division of Biostatistics, University of Minnesota, 55455, USA.
Ann Hum Genet. 2011 Mar;75(2):292-304. doi: 10.1111/j.1469-1809.2010.00619.x. Epub 2010 Nov 22.
Linkage detection of a trait involves detecting regions of the genome that influence the trait. A wide variety of statistical models are currently employed for linkage analysis of quantitative traits. Many of these models are developed under some assumptions of the trait distributions. Violation of the assumptions about the trait generally affects the type I error and power for linkage detection. In this paper, we have proposed a trait-model-free approach for linkage analysis of a quantitative trait in general pedigrees. The conditional segregation of marker alleles given the trait is modeled using a latent-variable logistic model. A likelihood-ratio test is used to test for linkage under our model. The main applicability of this approach lies in the fact that it always provides correct type I error no matter what the trait distribution is and thus can be used for nonnormal traits or for selected samples. By means of simulation studies, we have compared the power of our proposed model with existing approaches for nonnormal traits. The performance of these methods was also studied on a real dataset. We have demonstrated the usefulness of our approach in terms of power and robustness for linkage detection of quantitative traits in general pedigrees.
性状的连锁检测涉及检测基因组中影响该性状的区域。目前,各种各样的统计模型被用于数量性状的连锁分析。这些模型中的许多都是在性状分布的一些假设下开发的。违反关于性状的假设通常会影响连锁检测的I型错误和检验效能。在本文中,我们提出了一种无性状模型的方法,用于一般家系中数量性状的连锁分析。使用潜在变量逻辑模型对给定性状下标记等位基因的条件分离进行建模。在我们的模型下,使用似然比检验来检验连锁。这种方法的主要适用性在于,无论性状分布如何,它总能提供正确的I型错误,因此可用于非正态性状或选定样本。通过模拟研究,我们将我们提出的模型与现有非正态性状方法的检验效能进行了比较。还在一个真实数据集上研究了这些方法的性能。我们已经证明了我们的方法在一般家系中数量性状连锁检测的检验效能和稳健性方面的有用性。