Niu Tianhua, Ding Adam A, Kreutz Reinhold, Lindpaintner Klaus
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Genetics. 2005 Feb;169(2):1021-31. doi: 10.1534/genetics.103.019752.
The mapping of quantitative trait loci (QTL) is an important research question in animal and human studies. Missing data are common in such study settings, and ignoring such missing data may result in biased estimates of the genotypic effect and thus may eventually lead to errant results and incorrect inferences. In this article, we developed an expectation-maximization (EM)-likelihood-ratio test (LRT) in QTL mapping. Simulation studies based on two different types of phylogenetic models revealed that the EM-LRT, a statistical technique that uses EM-based parameter estimates in the presence of missing data, offers a greater statistical power compared with the ordinary analysis-of-variance (ANOVA)-based test, which discards incomplete data. We applied both the EM-LRT and the ANOVA-based test in a real data set collected from F2 intercross studies of inbred mouse strains. It was found that the EM-LRT makes an optimal use of the observed data and its advantages over the ANOVA F-test are more pronounced when more missing data are present. The EM-LRT method may have important implications in QTL mapping in experimental crosses.
数量性状基因座(QTL)定位是动物和人类研究中的一个重要研究问题。在这类研究中,缺失数据很常见,而忽略这些缺失数据可能会导致对基因型效应的估计产生偏差,最终可能导致错误的结果和推断。在本文中,我们开发了一种用于QTL定位的期望最大化(EM)似然比检验(LRT)。基于两种不同类型系统发育模型的模拟研究表明,EM-LRT(一种在存在缺失数据时使用基于EM的参数估计的统计技术)与丢弃不完整数据的基于普通方差分析(ANOVA)的检验相比,具有更强的统计功效。我们将EM-LRT和基于ANOVA的检验应用于从近交系小鼠品系的F2杂交研究中收集的一个真实数据集。结果发现,EM-LRT能最佳地利用观测数据,并且当存在更多缺失数据时,它相对于ANOVA F检验的优势更为明显。EM-LRT方法可能对实验杂交中的QTL定位具有重要意义。