A powerful genome-wide feasible approach to detect parent-of-origin effects in studies of quantitative traits
A powerful genome-wide feasible approach to detect parent-of-origin effects in studies of quantitative traits
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DOI：
10.1038/ejhg.2009.167
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发表时间：
2010-03-01
影响因子：
5.2
通讯作者：
Aulchenko, Yurii S.
中科院分区：
文献类型：
--
作者：
Belonogova, Nadezhda M.;Axenovich, Tatiana I.;Aulchenko, Yurii S.
目前，基因组印记在哺乳动物发育中的作用引起了广泛的兴趣。许多人类疾病，如癌症、肥胖、糖尿病和行为特征，都可能与印记基因有关。当寻找与复杂疾病相关的基因时，全基因组关联分析的能力可以通过将起源父母效应引入分析中来提高。对于数量性状，基于家系的TDT分析成功地实现了这样的方法。虽然有吸引力的几个原因，TDT为基础的测试是已知的是不太强大的方法的基础上测量基因型的方法。在这项研究中，我们描述了一种快速、强大的方法，用于使用测量的基因型框架在数量性状研究中检测起源父母效应。首先，对于每个位点的研究，我们估计的概率等位基因的父母的起源使用多点单倍型重建。接下来，我们在GRAMMAR的第二步（测量基因型方法的快速近似）中引入这些等位基因的亲本来源作为回归模型中的协变量。我们表明，与基于TDT的分析相比，我们的方法具有更高的功率来检测表现出父源效应的位点。此外，我们的方法适用于更广泛的数据，包括系谱结构，不是非常翔实的TDT。该方法在加性和显性模型下，在不存在原产地亲本效应的情况下均不会出现假阳性。由于该方法是快速GRAMMAR分析的扩展，因此它足够快以适合全基因组关联扫描。欧洲人类遗传学杂志（2010）18，379-384; doi：10.1038/ejhg.2009.167; 2009年10月7日在线发表
There is currently a lot of interest in the role of genomic imprinting in mammalian development. Many human diseases, such as cancer, obesity, diabetes and behavioral traits, may be related to imprinted genes. When searching for genes related to complex disorders, the power of genome-wide association analysis can be improved by introducing parent-of-origin effects into the analyses. For quantitative traits, family-based TDT analysis has successfully implemented such an approach. Although attractive for several reasons, TDT-based tests are known to be less powerful than methods based on measured genotype approaches. In this study, we describe a fast, powerful method for detecting parent-of-origin effects in studies of quantitative traits using a measured genotype framework. First, for each locus studied, we estimate the probabilities of an allele's parental origin using multipoint haplotype reconstruction. Next, we introduce the parental origin of these alleles as a covariate in regression models during the second step of GRAMMAR, a fast approximation to the measured genotype approach. We show that, compared with a TDT-based analysis, our method has a higher power to detect a locus exhibiting a parent-of-origin effect. Moreover, our method is applicable to a wider range of data, including pedigree structures that are not very informative for TDT. The method gives no false positives in the absence of parent-of-origin effects, under both additive and dominant models. As this method is an extension of the rapid GRAMMAR analysis, it is fast enough to be suitable for genome-wide association scans. European Journal of Human Genetics (2010) 18, 379-384; doi:10.1038/ejhg.2009.167; published online 7 October 2009