整合病例对照研究和传递不平衡检验(TDT)研究。

Integrating case-control and TDT studies.

作者信息

Kazeem G R, Farrall M

机构信息

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

出版信息

Ann Hum Genet. 2005 May;69(Pt 3):329-35. doi: 10.1046/j.1529-8817.2005.00156.x.

Abstract

Genetic-association studies are widely expected to unravel the genetic basis of complex diseases. The population-based case-control study, a commonly used approach for association studies, is subject to the problem of population admixture. Consequently, evidence of disease-marker associations obtained from such studies is ideally confirmed by alternative methods. The Transmission/Disequilibrium Test (TDT) is suitable to assess evidence of association obtained from case-control studies. Since data are increasingly available from both case-control and TDT studies of the same disease-marker association, it is useful to obtain a combined estimate of disease-marker association. The odds ratio is a commonly used measure of the magnitude of a disease-marker association that can be easily obtained in case-control studies. Here we show how an odds ratio estimate and its' associated standard error can be obtained from TDT results. Furthermore, we suggest a method for integrating results from case-control studies and the TDT to provide a combined estimate of disease-marker association. Such combined estimates can be used to contrast the results of the two studies and provides an overall picture of the effect size attributable to such polymorphism. An illustrative application is made to a published data set on type 2 diabetes.

摘要

人们普遍期望基因关联研究能够揭示复杂疾病的遗传基础。基于人群的病例对照研究是关联研究常用的方法,但存在人群混杂的问题。因此,从这类研究中获得的疾病标记物关联证据最好通过其他方法进行验证。传递/不平衡检验(TDT)适用于评估从病例对照研究中获得的关联证据。由于关于同一疾病标记物关联的病例对照研究和TDT研究的数据越来越多,因此获得疾病标记物关联的综合估计是很有用的。优势比是衡量疾病标记物关联程度的常用指标,在病例对照研究中很容易获得。在这里,我们展示了如何从TDT结果中获得优势比估计及其相关标准误。此外,我们提出了一种整合病例对照研究和TDT结果的方法,以提供疾病标记物关联的综合估计。这种综合估计可用于对比两项研究的结果,并提供归因于这种多态性的效应大小的总体情况。我们对已发表的2型糖尿病数据集进行了说明性应用。

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