Shete Sanjay, Beasley T Mark, Etzel Carol J, Fernández José R, Chen Jianfang, Allison David B, Amos Christopher I
Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Behav Genet. 2004 Mar;34(2):153-9. doi: 10.1023/B:BEGE.0000013729.26354.da.
Variance components analysis provides an efficient method for performing linkage analysis for quantitative traits. However, power and type 1 error of variance components-based likelihood ratio testing may be affected when phenotypic data are nonnormally distributed (especially with high values of kurtosis) and there is moderate to high correlation among the siblings. Winsorization can reduce the effect of outliers on statistical analyses. Here, we considered the effect of winsorization on variance components-based tests. We considered the likelihood ratio test (LRT), the Wald test, and some robust variance components tests. We compared these tests with Haseman-Elston least squares-based tests. We found that power to detect linkage is significantly increased after winsorization of the nonnormal phenotypes. Winsorization does not greatly diminish the type 1 error for the variance components-based tests for markedly nonnormal data. A robust version of the LRT that adjusts for sample kurtosis showed the best power for nonnormal data. Finally, phenotype winsorization of nonnormal data reduces the bias in estimation of the major gene variance component.
方差成分分析为进行数量性状的连锁分析提供了一种有效的方法。然而,当表型数据呈非正态分布(尤其是峰度值较高时)且同胞之间存在中度至高相关性时,基于方差成分的似然比检验的功效和I类错误可能会受到影响。缩尾法可以减少异常值对统计分析的影响。在此,我们考虑了缩尾法对基于方差成分检验的影响。我们考虑了似然比检验(LRT)、Wald检验以及一些稳健的方差成分检验。我们将这些检验与基于Haseman-Elston最小二乘法的检验进行了比较。我们发现,对非正态表型进行缩尾后,检测连锁的功效显著提高。对于明显非正态的数据,缩尾法不会大幅降低基于方差成分检验的I类错误。一种针对样本峰度进行调整的稳健版LRT对非正态数据显示出最佳功效。最后,对非正态数据进行表型缩尾可减少主基因方差成分估计中的偏差。