A powerful parent-of-origin effects test for qualitative traits incorporating control children in nuclear families
A powerful parent-of-origin effects test for qualitative traits incorporating control children in nuclear families
复制标题
对核心家庭中对照儿童的质量特征进行强大的原籍父母效应测试
DOI：
10.1038/jhg.2012.58
复制
发表时间：
2012-08-01
影响因子：
3.5
通讯作者：
Fung, Wing Kam
中科院分区：
文献类型：
--
作者：
Zhou, Ji-Yuan;Mao, Wei-Gao;Fung, Wing Kam
基因组印记是研究复杂性状时的一种重要表观遗传现象，通常通过检测等位基因的亲本来源效应来进行研究。基于父母双全的核心家庭的亲代不对称检验（PAT）及其处理缺失亲本基因型的扩展方法，对于此类任务既简单又有效。然而，这些方法仅使用核心家庭中的患病（受影响）子女，因此如果这些家庭中有对照（未患病）子女的信息，却没有充分利用。在本文中，我们提出了一种新的亲本来源效应检验方法C - PATu（PATu和1 - PATu的组合检验），该方法利用了有一方或双方父母的核心家庭中的对照子女和患病子女。C - PATu本质上是一个加权框架，其中基于所有对照子女及其父母的检验和基于所有患病子女及其父母的检验根据人群疾病患病率进行加权。模拟结果表明，所提出的检验在无亲本来源效应时能很好地控制检验水准，并且利用来自对照子女的额外信息提高了在印记备择假设下检验的效能。将C - PATu应用于弗雷明汉心脏研究数据集进一步表明了该检验在实际应用中的可行性。《人类遗传学杂志》（2012年）57卷，500 - 507页；doi:10.1038/jhg.2012.58；2012年5月31日在线发表
Genomic imprinting is an important epigenetic phenomenon in studying complex traits and has generally been examined by detecting parent-of-origin effects of alleles. The parental-asymmetry test (PAT) based on nuclear families with both parents and its extensions to deal with missing parental genotypes is simple and powerful for such a task. However, these methods only use case (affected) children in nuclear families and thus do not make full use of information on control (unaffected) children, if available, in these families. In this article, we propose a novel parent-of-origin effects test C-PATu (the combined test of PATu and 1-PATu) by using both the control and case children in nuclear families with one or both parents. C-PATu is essentially a weighted framework, in which the test based on all the control children and their parents and that based on all the case children and their parents are weighted according to the population disease prevalence. Simulation results demonstrate that the proposed tests control the size well under no parent-of-origin effects and using additional information from control children improves the power of the tests under the imprinting alternative. Application of C-PATu to a Framingham Heart Study data set further shows the feasibility in practical application of the test.