Goldstein D R, Dudoit S, Speed T P
Department of Statistics, University of California at Los Angeles, Los Angeles, CA 90095-1554, USA.
Genet Epidemiol. 2001 May;20(4):415-31. doi: 10.1002/gepi.1011.
Identification of genes involved in complex traits by traditional (lod score) linkage analysis is difficult due to many complicating factors. An unfortunate drawback of non-parametric procedures in general, though, is their low power to detect genetic effects. Recently, Dudoit and Speed [2000] proposed using a (likelihood-based) score test for detecting linkage with IBD data on sib pairs. This method uses the likelihood for theta, the recombination fraction between a trait locus and a marker locus, conditional on the phenotypes of the two sibs to test the null hypothesis of no linkage (theta = (1/2)). Although a genetic model must be specified, the approach offers several advantages. This paper presents results of simulation studies characterizing the power and robustness properties of this score test for linkage, and compares the power of the test to the Haseman-Elston and modified Haseman-Elston tests. The score test is seen to have impressively high power across a broad range of true and assumed models, particularly under multiple ascertainment. Assuming an additive model with a moderate allele frequency, in the range of p = 0.2 to 0.5, along with heritability H = 0.3 and a moderate residual correlation rho = 0.2 resulted in a very good overall performance across a wide range of trait-generating models. Generally, our results indicate that this score test for linkage offers a high degree of protection against wrong assumptions due to its strong robustness when used with the recommended additive model.
由于存在许多复杂因素，通过传统的（对数计分）连锁分析来识别与复杂性状相关的基因非常困难。然而，一般来说，非参数方法的一个不幸缺点是它们检测基因效应的能力较低。最近，杜多伊特和斯皮德[2000]提出使用一种（基于似然性的）计分检验来检测同胞对中基于IBD数据的连锁。该方法使用给定两个同胞表型条件下，性状位点与标记位点之间重组率θ的似然性，来检验无连锁（θ = 1/2）的零假设。尽管必须指定一个遗传模型，但该方法具有几个优点。本文展示了模拟研究的结果，这些结果刻画了这种连锁计分检验的功效和稳健性特性，并将该检验的功效与哈斯曼 - 埃尔斯顿检验和改进的哈斯曼 - 埃尔斯顿检验进行了比较。在广泛的真实模型和假设模型中，尤其是在多重确定的情况下，计分检验的功效都非常高。假设一个具有中等等位基因频率（p在0.2至0.5范围内）的加性模型，同时遗传力H = 0.3且残差相关性适中（ρ = 0.2），在广泛的性状生成模型中会产生非常好的总体表现。一般来说，我们的结果表明，这种连锁计分检验由于在与推荐的加性模型一起使用时具有很强的稳健性，所以能高度防止错误假设。
