The transmission/disequilibrium test: history, subdivision, and admixture.
The transmission/disequilibrium test: history, subdivision, and admixture.
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DOI：
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发表时间：
1995-08
影响因子：
9.8
通讯作者：
W. Ewens;R. Spielman
中科院分区：
文献类型：
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作者：
W. Ewens;R. Spielman
疾病与遗传标记的关联通常被认为是与疾病易感性相关联的初步迹象。然而，即使在没有连锁的情况下，种群的细分和混合也可能导致疾病关联。在以前的一篇论文中，我们描述了遗传标记和疾病易感性之间的连锁(和连锁不平衡)测试；只有在存在关联的情况下，该测试才能检测到连锁。这种传递/不平衡检验(TDT)是利用标记杂合双亲的标记等位基因传递给受影响的后代的数据进行的。TDT是一种有效的连锁和关联测试，即使这种关联是由种群细分和混合引起的。在前文中，我们没有明确考虑近代史对人口结构的影响。在这里，我们通过详细检查细分和混合的影响来扩展先前的结果，这被视为种群历史中的过程。我们描述了这些过程的两个模型。对于这两个模型，我们分析了(A)TDT作为标记与疾病之间的联系(和关联)的检验的性质，以及(B)传统的权变统计量与家庭数据一起用于检验人群关联的性质。我们证明了当存在细分或混合时，偶合检验统计量不具有X~2分布。相反，无论群体历史如何，TDT仍然是连锁假说的一个有效的X~2统计量。
Disease association with a genetic marker is often taken as a preliminary indication of linkage with disease susceptibility. However, population subdivision and admixture may lead to disease association even in the absence of linkage. In a previous paper, we described a test for linkage (and linkage disequilibrium) between a genetic marker and disease susceptibility; linkage is detected by this test only if association is also present. This transmission/disequilibrium test (TDT) is carried out with data on transmission of marker alleles from parents heterozygous for the marker to affected offspring. The TDT is a valid test for linkage and association, even when the association is caused by population subdivision and admixture. In the previous paper, we did not explicitly consider the effect of recent history on population structure. Here we extend the previous results by examining in detail the effects of subdivision and admixture, viewed as processes in population history. We describe two models for these processes. For both models, we analyze the properties of (a) the TDT as a test for linkage (and association) between marker and disease and (b) the conventional contingency statistic used with family data to test for population association. We show that the contingency test statistic does not have a chi 2 distribution if subdivision or admixture is present. In contrast, the TDT remains a valid chi 2 statistic for the linkage hypothesis, regardless of population history.