Extensive studies have been conducted on the analysis of genome function, especially on the expression quantitative trait loci (eQTL). These studies offered promising results for characterization of the functional sequencing variation and understanding of the basic processes of gene regulation. Parent of origin effect (POE) is an important epigenetic phenomenon describing that the expression of certain genes depends on their allelic parent-of-origin and it is known to play important roles in human complex diseases. However, traditional eQTL mapping approaches do not allow for the detection of imprinting, or they focus on modeling the additive genetic effect thereby ignoring the estimation of the dominance genetic effect. In this study, we proposed a statistical framework to test the additive and dominance genetic effects of the candidate eQTLs along with detection of the POE with a functional model and an orthogonal model for RNA-seq data. We demonstrated the desirable power and preserved Type I errors of the methods in most scenarios, especially the orthogonal model with un-biased estimation of the genetic effects and over-dispersion of the RNA-seq data. The application to a HapMap project trio dataset validated existing imprinting genes and discovered two novel imprinting genes with potential dominance genetic effect and RB1 and IGF1R genes. This study provides new insights into the next generation statistical modeling of eQTL mapping for better understanding of the genetic architecture underlying the mechanisms of gene expression regulation.

已经对基因组功能的分析进行了广泛的研究，特别是在表达数量性状基因座（eQTL）的表达上。这些研究为功能序列变异的表征和基因调控的基本过程的理解提供了令人鼓舞的结果。起源亲本效应（POE）是一种重要的表观遗传现象，描述某些基因的表达取决于其等位基因的起源亲本，并且已知在人类复杂疾病中起重要作用。但是，传统的eQTL映射方法不允许检测印迹，或者它们专注于对累加遗传效应进行建模，从而忽略了对优势遗传效应的估计。在这个研究中，我们提出了一个统计框架来测试候选eQTL的加性和优势遗传效应，以及使用功能模型和正交模型对RNA-seq数据进行POE检测。我们证明了在大多数情况下该方法的理想功效和保留的I型错误，尤其是正交模型，该模型具有无偏估计的遗传效应和RNA-seq数据的过度分散。在HapMap项目三重数据集上的应用验证了现有的印迹基因，并发现了两个具有潜在优势遗传效应的新型印迹基因。尤其是正交模型，可以无偏估计遗传效应和RNA-seq数据的过度分散。在HapMap项目三重数据集上的应用验证了现有的印迹基因，并发现了两个具有潜在优势遗传效应的新型印迹基因。尤其是正交模型，可以无偏估计遗传效应和RNA-seq数据的过度分散。在HapMap项目三重数据集上的应用验证了现有的印迹基因，并发现了两个具有潜在优势遗传效应的新型印迹基因。RB1和IGF1R基因。这项研究提供了对eQTL映射的下一代统计模型的新见解，以更好地理解基因表达调控机制背后的遗传结构。