Testing untyped alleles (TUNA) - Applications to genome-wide association studies
Testing untyped alleles (TUNA) - Applications to genome-wide association studies
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DOI：
10.1002/gepi.20182
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发表时间：
2006-12-01
影响因子：
2.1
通讯作者：
Nicolae, Dan L.
中科院分区：
文献类型：
--
作者：
Nicolae, Dan L.
在分析全基因组关联研究的数据时进行的大量测试对检测风险变体的能力有很大影响，并且需要指定待测试的最佳假设集的分析策略。我们提出了一个全基因组的策略，是基于一个自由度的测试，所有的基因型变异，并为所有的未分型的变异，有足够的信息，在观察到的数据。使用来自参考数据库如HapMap（The International HapMap Consortium [2003] Nature 426：789-796）的连锁不平衡和单倍型频率的多基因座测量发现待测试的未分型变体组。我们介绍了一种新的统计测试差异等位基因频率的未分型的变化是基于线性组合的可估计的单倍型频率。还描述了用于发现待用于测试未分型等位基因的基因分型标记物的集合的算法，以及并入在研究数据中观察到但在参考数据库中未观察到的单倍型的方式。所提出的测试策略可以用作全基因组关联数据分析的第一步，并且，由于每个执行的测试都针对标记物，因此它可以用于在后续研究中指定多态性的基因型集合。所述方法还为联合分析在不同平台上进行的研究的数据提供了一个工具。Genet.流行病学30：718-727，2006. (c)2006 Wiley-Liss，Inc.
The large number of tests performed in analyzing data from genome-wide association studies has a large impact on the power of detecting risk variants, and analytic strategies specifying the optimal set of hypotheses to be tested are necessary. We propose a genome-wide strategy that is based on one degree of freedom tests for all the genotyped variants, and for all the untyped variants for which there is sufficient information in the observed data. The set of untyped variants to be tested is found using multi-locus measures of linkage clisequilibrium and haplotype frequencies from a reference database such as HapMap (The International HapMap Consortium [2003] Nature 426:789-796). We introduce a novel statistic for testing differences in allele frequencies for untyped variation that is based on linear combinations of estimable haplotype frequencies. Algorithms for finding the sets of genotyped markers to be used in testing an untyped allele, and ways of incorporating haplotypes observed in the study data but not in the reference database are also described. The proposed testing strategy can be used as the first step in the analysis of genome-wide association data, and, because every performed test is directed to a marker, it can be used to specify the set of polymorphisms to genotype in follow-up studies. The described methodology provides also a tool for joint analysis of data from studies done on different platforms. Genet. Epidemiol. 30:718-727, 2006. (c) 2006 Wiley-Liss, Inc.