Adding further power to the Haseman and Elston method for detecting linkage in larger sibships: Weighting sums and differences
Adding further power to the Haseman and Elston method for detecting linkage in larger sibships: Weighting sums and differences
复制标题
DOI：
10.1159/000072312
复制
发表时间：
2003-01-01
期刊：
影响因子：
1.8
通讯作者：
Elston, RC
中科院分区：
文献类型：
--
作者：
Shete, S;Jacobs, KB;Elston, RC
哈斯曼和埃尔斯顿(H-E)提出了一种稳健的测试来检测数量性状和遗传标记之间的联系。在他们的方法中，同胞对性状差异的平方与同胞对血统相同的基因座上等位基因的估计比例进行了回归。这种方法最近得到了改进，将因变量从平方差改为同胞对性状值的均值校正乘积，这是一种表明连锁的显著正回归。由于出现了原始检验更强大的情况，当因变量改变为同胞对平方性状差异和同胞对平均校正平方和的加权平均时，WE方法发生了进一步的改进。在这里，我们提出了一种对较大的兄弟关系执行这种加权的最佳方法，允许兄弟关系内的对之间的相关性。考虑到同胞对之间的相关性，最优权重与分别基于同胞对性状平方和的两个不同回归所获得的残差方差成反比。将所提出的方法与现有的大型子船H-E方法的扩展方法进行了比较。通过使用广义估计方程方法和方差的稳健夹心估计或蒙特卡罗置换检验，可以改善对任意大小的子项的I类错误概率的控制。版权所有(C)2003 S.Karger AG，基数I性状差异和平方同胞对均值已更正。
Haseman and Elston (H-E) proposed a robust test to detect linkage between a quantitative trait and a genetic marker. In their method the squared sib-pair trait difference is regressed on the estimated proportion of alleles at a locus shared identical by descent by sib pairs. This method has recently been improved by changing the dependent variable from the squared difference to the mean-corrected product of the sib-pair trait values, a significantly positive regression indicating linkage. Because situations arise in which the original test is more powerful, a further improvement of the WE method occurs when the dependent variable is changed to a weighted average of the squared sib-pair trait difference and the squared sib-pair mean-corrected trait sum. Here we propose an optimal method of performing this weighting for larger sibships, allowing for the correlation between pairs within a sibship. The optimal weights are inversely proportional to the residual variances obtained from the two different regressions based on the squared sib-pair trait sums, respectively, allowing for correlations among sib pairs. The proposed method is compared with the existing extension of the H-E approach for larger sibships. Control of the type I error probabilities for sibships of any size can be improved by using a generalized estimating equation approach and the robust sandwich estimate of the variance, or a Monte-Carlo permutation test. Copyright (C) 2003 S. Karger AG, Base I trait differences and the squared sib-pair mean-corrected.