Department of Statistics and Actuarial Science, The University of Hong Kong, Hong Kong.
Bioinformatics. 2011 Sep 15;27(18):2571-7. doi: 10.1093/bioinformatics/btr443. Epub 2011 Jul 28.
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.
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.
Supplementary data are available at Bioinformatics online.
对于二等位标记基因座，传递不平衡检验（TDT）是一种用于遗传研究的简单而强大的设计。TDT 最初是为有双亲可用的（完整核家族）家庭提出的，并且进一步扩展到 1-TDT 用于只有一个双亲可用的家庭（不完全核家族）。目前，对亲本印迹对遗传力的影响的日益关注表明，将印迹效应纳入关联变体的映射中非常重要。
在本文中，我们将 TDT 型统计扩展到纳入印迹效应，并在关联研究的一般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家庭的设计的性质，不需要假设哈迪-温伯格平衡。此外，所提出的方法适用于有一个或多个受影响孩子的完整和不完全核家庭。在模拟研究中，我们在各种情况下验证了所提出的测试统计数据的有效性，并将所提出的统计数据的功效与一些现有测试统计数据进行了比较。结果表明，我们的方法在存在印迹效应的情况下大大提高了检测关联的功效。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进一步证明了我们方法的优势。
补充资料可在生物信息学在线获取。
