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首页> 外文期刊>Annals of Human Genetics >Genotype-Based Association Analysis Using Discordant Pairs: A Penetrance Odds Ratio Approach
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Genotype-Based Association Analysis Using Discordant Pairs: A Penetrance Odds Ratio Approach

机译:基于基因型的使用不和谐对的关联分析:一种穿透率比方法

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Genotypic counts of paired relatives discordant for a complex late-onset disease are often used to test for genetic association. The power of the various statistical test options, when data on covariates are unavailable, has been the focus of recent research. Comparison of the Cochran-Armitage, Bhapkar, and McNemar tests indicates that none is superior to the others in all cases. Using an alternative approach, we found that the theoretical genotypic frequencies of the discordant pairs depend only on the penetrance odds ratios, after conditioning. These odds ratios can be estimated by maximizing a product binomial likelihood and provide insight into the mode of inheritance. We identified cases where exact maximum likelihood (ML) estimates can be explicitly obtained. This approach led us to two tests for association which depend on likelihood ratio (LR) or score statistics. We quantified the power of these tests analytically and examined their performance through simulation. We explored the utility of these tests with an example from the literature-the association between complement factor H (CFH) polymorphisms and age-related macular degeneration. The LR and Score tests serve as simple and effective ways of interpreting paired case-control data sets. ? 2013 Blackwell Publishing Ltd/University College London.
机译:复杂的迟发性疾病不一致的成对亲属的基因型计数通常用于测试遗传关联。当无法获得有关协变量的数据时,各种统计检验选项的功能已成为近期研究的重点。 Cochran-Armitage,Bhapkar和McNemar检验的比较表明,在所有情况下,没有一个优于其他。使用替代方法,我们发现条件处理后,不和谐对的理论基因型频率仅取决于外显率比。这些比值比可以通过最大化乘积二项式似然来估计,并提供对继承模式的深入了解。我们确定了可以明确获得确切最大似然(ML)估计的情况。这种方法使我们进行了两种关联测试,这些测试取决于似然比(LR)或得分统计。我们通过分析量化了这些测试的功能,并通过仿真检查了它们的性能。我们以文献为例探讨了这些测试的效用-补体因子H(CFH)多态性与年龄相关性黄斑变性之间的关联。 LR和Score检验是解释配对病例对照数据集的简单有效的方法。 ? 2013布莱克韦尔出版有限公司/伦敦大学学院。

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