Robust TDT-type candidate-gene association tests
Robust TDT-type candidate-gene association tests
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DOI：
10.1046/j.1469-1809.2002.00104.x
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发表时间：
2002-03-01
影响因子：
1.9
通讯作者：
Gastwirth, JL
中科院分区：
文献类型：
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作者：
Zheng, G;Freidlin, B;Gastwirth, JL
在研究遗传标记与疾病之间的关联时，传递不平衡检验（TDT）已成为标准程序。它最初被引入作为在关联存在的情况下对连锁的测试，并且可以用作测试。对于联想突袭机的适当假设。候选基因与疾病之间关联的TDT检验的功效取决于潜在的遗传模型，如果加性模型成立，则TDT是最佳检验。对于给定的遗传模式（例如显性或隐性），已经获得了相关的方法。然而，通常真实的模型是未知的，并且选择单一的分析方法是有问题的，因为如果另一个遗传模型是真实的，则使用对一个遗传模型最优的检验通常会导致功效的实质性损失。效率稳健性的一般方法提出了两种类型的稳健程序，我们将其应用于TDT型关联检验。当替代模型的合理范围很宽时（例如显性到隐性），我们的结果表明，几个检验统计量的最大值（MIX），每个检验统计量对于不同的模型都是最优的，在所有遗传模型下都具有良好的功效。在可能的模型集可以缩小的情况下（例如，通过加性占主导地位），简单的线性组合也会表现出色。一般来说，当遗传方式未知时，MAX比TDT具有更好的幂特性用于候选基因的研究。
In studies of association between genetic markers and a disease, the transmission disequilibrium test (TDT) has become a standard procedure. It was introduced originally as a test for linkage in the presence of association and can be used as a teat. for association raider appropriate assumptions. The power of the TDT test for association between a candidate gene and disease depends on the underlying genetic model and the TDT is the optimal test if the additive model holds. Related methods have been obtained for a given mode of inheritance (e.g. dominant or recessive). Quite often, however, the true model is unknown and selection of a single method of analysis is problematic, since use of a test optimal for one genetic model usually leads to a substantial loss of power if another genetic model is the true one. The general approach of efficiency robustness has suggested two types of robust procedures, which we apply to TDT-type association tests. When the plausible range of alternative models is wide (e.g. dominant through recessive) our results indicate that the maximum (MIX) of several test statistics, each of which is optimal for quite different models has good power under all genetic models. In situations where the set of possible models can be narrowed (e.g. dominant through additive) a simple linear combination also performs hell. In general, the MAX has better power properties than the TDT for the study of candidate genes when the mode of inheritance is unknown.