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用于混合模型的似然比检验及其在基因连锁分析中的应用。

Likelihood ratio testing for admixture models with application to genetic linkage analysis.

作者信息

Di Chong-Zhi, Liang Kung-Yee

机构信息

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M2-B500, Seattle, Washington 98109, USA.

出版信息

Biometrics. 2011 Dec;67(4):1249-59. doi: 10.1111/j.1541-0420.2011.01574.x. Epub 2011 Mar 8.

Abstract

We consider likelihood ratio tests (LRT) and their modifications for homogeneity in admixture models. The admixture model is a two-component mixture model, where one component is indexed by an unknown parameter while the parameter value for the other component is known. This model is widely used in genetic linkage analysis under heterogeneity in which the kernel distribution is binomial. For such models, it is long recognized that testing for homogeneity is nonstandard, and the LRT statistic does not converge to a conventional χ(2)  distribution. In this article, we investigate the asymptotic behavior of the LRT for general admixture models and show that its limiting distribution is equivalent to the supremum of a squared Gaussian process. We also discuss the connection and comparison between LRT and alternative approaches such as modifications of LRT and score tests, including the modified LRT (Fu, Chen, and Kalbfleisch, 2006, Statistica Sinica 16, 805-823). The LRT is an omnibus test that is powerful to detect general alternative hypotheses. In contrast, alternative approaches may be slightly more powerful to detect certain type of alternatives, but much less powerful for others. Our results are illustrated by simulation studies and an application to a genetic linkage study of schizophrenia.

摘要

我们考虑似然比检验(LRT)及其在混合模型中用于齐性检验的修正方法。混合模型是一种双组分混合模型,其中一个组分由一个未知参数索引,而另一个组分的参数值是已知的。该模型在遗传连锁分析中广泛应用于核分布为二项分布的异质性情况。对于这类模型,长期以来人们都认识到齐性检验是非标准的,并且LRT统计量并不收敛到传统的χ²分布。在本文中,我们研究了一般混合模型中LRT的渐近行为,并表明其极限分布等同于一个平方高斯过程的上确界。我们还讨论了LRT与其他替代方法(如LRT的修正和得分检验)之间的联系与比较,包括修正的LRT(Fu、Chen和Kalbfleisch,2006年,《统计学报》16卷,805 - 823页)。LRT是一种综合检验,对于检测一般的备择假设很有效。相比之下,替代方法可能在检测某些类型的备择假设时稍微更有效,但对其他备择假设的效力则要低得多。我们通过模拟研究和对精神分裂症遗传连锁研究的应用来说明我们的结果。

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本文引用的文献

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Biometrics. 2011 Mar;67(1):182-93. doi: 10.1111/j.1541-0420.2010.01409.x.
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