A test for linkage and association in general pedigrees: The pedigree disequilibrium test
A test for linkage and association in general pedigrees: The pedigree disequilibrium test
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DOI：
10.1086/302957
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发表时间：
2000-07-01
影响因子：
9.8
通讯作者：
Kaplan, NL
中科院分区：
文献类型：
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作者：
Martin, ER;Monks, SA;Kaplan, NL
基于家庭的连锁不平衡测试通常基于核家庭数据，包括受影响的个体及其父母或其未受影响的兄弟姐妹。此类测试的一个局限性是，当使用来自较大血统的相关核心家庭的数据时，它们通常不是有效的关联测试。在测试连锁不平衡时，标准方法需要从任何扩展的血统中选择一个单个核家族。通常，数据可用于较大的血统，并且希望对可以使用所有潜在信息数据的链接不平衡测试有效测试。在这项研究中，我们介绍了血统不平衡测试（PDT），用于分析一般谱系中的连锁不平衡。 PDT可以使用来自扩展血统的相关核心家庭的数据，即使存在人口子结构，也是有效的。使用计算机模拟，我们证明了当使用渐近分布来评估显着性并检查统计能力时，测试的有效性。功率模拟表明，当可以使用扩展的血统数据时，可以通过使用PDT而不是仅使用数据子集的现有方法来实现大量功率。此外，即使对未受影响的个体的分类错误，PDT仍然更强大。我们的模拟表明，即使数据由没有扩展家庭信息的独立家庭组成，使用PDT也可能存在优势。因此，PDT提供了连锁不平衡的一般测试，可以广泛应用于不同的数据结构。
Family-based tests of linkage disequilibrium typically are based on nuclear-family data including affected individuals and their parents or their unaffected siblings. A limitation of such tests is that they generally are not valid tests of association when data from related nuclear families from larger pedigrees are used. Standard methods require selection of a single nuclear family from any extended pedigrees when testing for linkage disequilibrium. Often data are available for larger pedigrees, and it would be desirable to have a valid test of linkage disequilibrium that can use all potentially informative data. In this study, we present the pedigree disequilibrium test (PDT) for analysis of linkage disequilibrium in general pedigrees. The PDT can use data from related nuclear families from extended pedigrees and is valid even when there is population substructure. Using computer simulations, we demonstrated validity of the test when the asymptotic distribution is used to assess the significance, and examined statistical power. Power simulations demonstrate that, when extended pedigree data are available, substantial gains in power can be attained by use of the PDT rather than existing methods that use only a subset of the data. Furthermore, the PDT remains more powerful even when there is misclassification of unaffected individuals. Our simulations suggest that there may be advantages to using the PDT even if the data consist of independent families without extended family information. Thus, the PDT provides a general test of linkage disequilibrium that can be widely applied to different data structures.