Mao Yongcai, London Nicole R, Ma Li, Dvorkin Daniel, Da Yang
Department of Animal Science, University of Minnesota, Saint Paul, Minnesota 55108, USA.
Physiol Genomics. 2006 Dec 13;28(1):46-52. doi: 10.1152/physiolgenomics.00096.2006. Epub 2006 Aug 29.
Epistasis effects (gene interactions) have been increasingly recognized as important genetic factors underlying complex traits. The existence of a large number of single nucleotide polymorphisms (SNPs) provides opportunities and challenges to screen DNA variations affecting complex traits using a candidate gene analysis. In this article, four types of epistasis effects of two candidate gene SNPs with Hardy-Weinberg disequilibrium (HWD) and linkage disequilibrium (LD) are considered: additive x additive, additive x dominance, dominance x additive, and dominance x dominance. The Kempthorne genetic model was chosen for its appealing genetic interpretations of the epistasis effects. The method in this study consists of extension of Kempthorne's definitions of 35 individual genetic effects to allow HWD and LD, genetic contrasts of the 35 extended individual genetic effects to define the 4 epistasis effects, and a linear model method for testing epistasis effects. Formulas to predict statistical power (as a function of contrast heritability, sample size, and type I error) and sample size (as a function of contrast heritability, type I error, and type II error) for detecting each epistasis effect were derived, and the theoretical predictions agreed well with simulation studies. The accuracy in estimating each epistasis effect and rates of false positives in the absence of all or three epistasis effects were evaluated using simulations. The method for epistasis testing can be a useful tool to understand the exact mode of epistasis, to assemble genome-wide SNPs into an epistasis network, and to assemble all SNP effects affecting a phenotype using pairwise epistasis tests.
上位性效应（基因相互作用）已日益被视为复杂性状背后的重要遗传因素。大量单核苷酸多态性（SNP）的存在，为利用候选基因分析筛选影响复杂性状的DNA变异带来了机遇和挑战。本文考虑了具有哈迪 - 温伯格不平衡（HWD）和连锁不平衡（LD）的两个候选基因SNP的四种上位性效应类型：加性×加性、加性×显性、显性×加性和显性×显性。选择肯普索恩遗传模型是因其对上位性效应具有吸引人的遗传学解释。本研究方法包括将肯普索恩对35种个体遗传效应的定义进行扩展以允许HWD和LD，对这35种扩展后的个体遗传效应进行遗传对比以定义4种上位性效应，以及用于检验上位性效应的线性模型方法。推导了预测检测每种上位性效应的统计功效（作为对比遗传力、样本量和I型错误的函数）和样本量（作为对比遗传力、I型错误和II型错误的函数）的公式，理论预测与模拟研究结果吻合良好。通过模拟评估了在不存在所有或三种上位性效应时估计每种上位性效应的准确性和假阳性率。用于上位性检验的方法可以成为理解上位性的确切模式、将全基因组SNP组装成上位性网络以及使用成对上位性检验组装影响表型的所有SNP效应的有用工具。
