BACKGROUND Family-based design is one of the most popular designs in genetic studies. Transmission disequilibrium test (TDT) for family trio design is optimal only under the additive trait model and may lose power under the other trait models. The TDT-type tests are powerful only when the underlying trait model is correctly specified. Usually, the true trait model is unknown, and the selection of the TDT-type test is problematic. Several methods, which are robust against the mis-specification of the trait model, have been proposed. In this paper, we propose a new efficiency robust procedure for family trio design, namely, the weighted TDT (WTDT) test. METHODS We combine information of the largest two TDT-type tests by using weights related to the three TDT-type tests and take the weighted sum as the test statistic. RESULTS Simulation results demonstrate that WTDT has power close to, but much more robust than, the optimal TDT-type test based on a single trait model. WTDT also outperforms other efficiency robust methods in terms of power. Applications to real and simulated data from Genetic Analysis Workshop (GAW15) illustrate the practical application of the WTDT method. CONCLUSION WTDT is not only efficiency robust to model mis-specifications but also efficiency robust against mis-specifications of risk allele.

中文翻译：

---

家庭三重奏协会设计的加权传输不平衡测试。

背景技术基于家庭的设计是遗传研究中最受欢迎的设计之一。家庭三重奏设计的传输不平衡测试（TDT）仅在加性特征模型下是最佳的，而在其他特征模型下可能会失去功能。仅当正确指定了基础特征模型时，TDT类型的测试才具有强大的功能。通常，真正的特征模型是未知的，并且TDT型测试的选择存在问题。已经提出了几种对特征模型的错误指定具有鲁棒性的方法。在本文中，我们提出了一种新的针对家庭三重奏设计的高效鲁棒程序，即加权TDT（WTDT）测试。方法我们通过使用与三个TDT类型测试相关的权重来合并最大的两个TDT类型测试的信息，并将加权总和作为测试统计量。结果仿真结果表明，WTDT具有与基于单个特征模型的最佳TDT类型测试相近的功能，但功能强大得多。WTDT在功率方面也优于其他效率稳健的方法。遗传分析研讨会（GAW15）对真实和模拟数据的应用说明了WTDT方法的实际应用。结论WTDT不仅对模型错误规范有效，而且对风险等位基因错误规范有效。