A sibship test for linkage in the presence of association: The sib transmission/disequilibrium test
A sibship test for linkage in the presence of association: The sib transmission/disequilibrium test
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DOI：
10.1086/301714
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发表时间：
1998-02-01
影响因子：
9.8
通讯作者：
Ewens, WJ
中科院分区：
文献类型：
--
作者：
Spielman, RS;Ewens, WJ
利用遗传标记的连锁分析已经成功地定位了许多单基因人类疾病的基因。然而，在复杂疾病的研究中，依赖于连锁不平衡(同时存在连锁和关联)的测试往往比仅依赖于连锁的测试更有效。这一优势通过传输/不平衡测试(TDT)得到了说明。TDT需要受影响的个人及其父母的数据(标记基因类型)；然而，对于某些疾病，来自父母的数据可能很难或不可能获得。在本文中，我们描述了一种称为“同胞TDT”(或“S-TDT”)的方法，它通过使用来自未受影响的同胞而不是来自父母的标记数据来克服这一问题，从而允许将TDT的原理应用于没有父母资料的同胞。在一个单一的家庭集合中，可能有一些只能由TDT分析，而另一些适合由S TDT分析。我们展示了如何在一个整体TDT类型的程序中联合使用所有数据，该程序在存在关联的情况下测试关联，这些TDT的扩展将对晚发型疾病的研究有价值，例如非胰岛素依赖型糖尿病、心血管疾病和其他与衰老相关的疾病。
Linkage analysis with genetic markers has been successful in the localization of genes for many monogenic human diseases. In studies of complex diseases, however, tests that rely on linkage disequilibrium (the simultaneous presence of linkage and association) are often more powerful than those that rely on linkage alone. This advantage is illustrated by the transmission/disequilibrium test (TDT). The TDT requires data (marker genotypes) for affected individuals and their parents; for some diseases, however, data from parents may be difficult or impossible to obtain. In this article, we describe a method, called the "sib TDT" (or "S-TDT"), that overcomes this problem by use of marker data from unaffected sibs instead of from parents, thus allowing application of the principle of the TDT to sibships without parental data. In a single collection of families, there might be some that can be analyzed only by the TDT and others that are suitable for analysis by the S-TDT. We show how all the data may be used jointly in one overall TDT-type procedure that tests for linkage in the presence of association, These extensions of the TDT will be valuable for the study of diseases of late onset, such as non-insulin-dependent diabetes, cardiovascular diseases, and other diseases associated with aging.