Weighted Transmission Disequilibrium Test for Family Trio Association Design.

IF 1.1 4区生物学 Q4 GENETICS & HEREDITY

Human Heredity Pub Date : 2018-01-01 Epub Date: 2019-03-13 DOI:10.1159/000494353

Hongyan Fang, Yaning Yang, Ling Chen

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引用次数: 0

Abstract

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.

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家庭三人关联设计的加权传递不均衡检验。

背景:基于家族的设计是基因研究中最流行的设计之一。遗传不平衡检验(TDT)仅在加性性状模型下最优，在其他性状模型下可能失效。tdt类型测试只有在正确指定底层特征模型时才有效。通常，真正的性状模型是未知的，tdt型检验的选择是有问题的。提出了几种对特征模型的错误描述具有鲁棒性的方法。在本文中，我们提出了一种新的高效鲁棒的三族设计程序，即加权TDT (WTDT)检验。方法:利用三个tdt型检验的相关权值，将最大的两个tdt型检验的信息进行组合，并以加权和作为检验统计量。结果:仿真结果表明，WTDT的功率接近于基于单一性状模型的最优tdt类型测试，但鲁棒性要高得多。WTDT在功率方面也优于其他效率稳健的方法。对遗传分析研讨会(GAW15)的真实和模拟数据的应用说明了WTDT方法的实际应用。结论:WTDT不仅对模型错配具有效率鲁棒性，而且对风险等位基因错配具有效率鲁棒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Heredity 生物-遗传学

CiteScore

2.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Gathering original research reports and short communications from all over the world, ''Human Heredity'' is devoted to methodological and applied research on the genetics of human populations, association and linkage analysis, genetic mechanisms of disease, and new methods for statistical genetics, for example, analysis of rare variants and results from next generation sequencing. The value of this information to many branches of medicine is shown by the number of citations the journal receives in fields ranging from immunology and hematology to epidemiology and public health planning, and the fact that at least 50% of all ''Human Heredity'' papers are still cited more than 8 years after publication (according to ISI Journal Citation Reports). Special issues on methodological topics (such as ‘Consanguinity and Genomics’ in 2014; ‘Analyzing Rare Variants in Complex Diseases’ in 2012) or reviews of advances in particular fields (‘Genetic Diversity in European Populations: Evolutionary Evidence and Medical Implications’ in 2014; ‘Genes and the Environment in Obesity’ in 2013) are published every year. Renowned experts in the field are invited to contribute to these special issues.