A powerful approach for association analysis incorporating imprinting effects

A powerful approach for association analysis incorporating imprinting effects
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结合印记效应的关联分析的强大方法

DOI：
10.1093/bioinformatics/btr443
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发表时间：
2011-09-15
期刊：
BIOINFORMATICS
影响因子：
5.8
通讯作者：
Fung, Wing Kam
Fung, Wing Kam
中科院分区：
生物学3区
文献类型：
--
作者：
Xia, Fan;Zhou, Ji-Yuan;Fung, Wing Kam

文献摘要

被引文献

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动机 对于双等位标记基因座，传递不平衡检验 (TDT) 是一种简单而强大的遗传研究设计。 TDT 最初建议用于有双亲的家庭（完全核心家庭），并进一步扩展到 1-TDT，用于只有双亲之一的家庭（不完全核心家庭）。目前，人们越来越关注亲本印记对遗传力的影响，这表明将印记效应纳入关联变异映射的重要性。 结果 在本文中，我们扩展了 TDT 型统计以纳入印记效应，并在关联研究的通用两阶段框架中开发了一系列新的测试统计。我们的测试统计数据具有基于族的设计的性质，无需假设哈迪-温伯格平衡。此外，所提出的方法还适应具有一名或多名受影响儿童的完整和不完整的核心家庭。在模拟研究中，我们验证了所提出的检验统计量在各种场景下的有效性，并将所提出的统计量与一些现有的检验统计量的功效进行了比较。结果表明，我们的方法极大地提高了在存在印记效应的情况下检测关联的能力。我们通过将所提出的测试统计数据应用于类风湿关节炎数据集来进一步证明我们的方法的优势。 联系方式 wingfung@hku.hk 补充信息 补充数据可在生物信息学在线获取。
MOTIVATION For a diallelic marker locus, the transmission disequilibrium test (TDT) is a simple and powerful design for genetic studies. The TDT was originally proposed for use in families with both parents available (complete nuclear families) and has further been extended to 1-TDT for use in families with only one of the parents available (incomplete nuclear families). Currently, the increasing interest of the influence of parental imprinting on heritability indicates the importance of incorporating imprinting effects into the mapping of association variants. RESULTS In this article, we extend the TDT-type statistics to incorporate imprinting effects and develop a series of new test statistics in a general two-stage framework for association studies. Our test statistics enjoy the nature of family-based designs that need no assumption of Hardy-Weinberg equilibrium. Also, the proposed methods accommodate complete and incomplete nuclear families with one or more affected children. In the simulation study, we verify the validity of the proposed test statistics under various scenarios, and compare the powers of the proposed statistics with some existing test statistics. It is shown that our methods greatly improve the power for detecting association in the presence of imprinting effects. We further demonstrate the advantage of our methods by the application of the proposed test statistics to a rheumatoid arthritis dataset. CONTACT wingfung@hku.hk SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.