Da Costa E Silva Luciano, Wang Shengchu, Zeng Zhao-Bang
Department of Statistics & Bioinformatics Research Center, North Carolina State University, Raleigh 27695-7566, USA.
BMC Genet. 2012 Aug 1;13:67. doi: 10.1186/1471-2156-13-67.
Although many experiments have measurements on multiple traits, most studies performed the analysis of mapping of quantitative trait loci (QTL) for each trait separately using single trait analysis. Single trait analysis does not take advantage of possible genetic and environmental correlations between traits. In this paper, we propose a novel statistical method for multiple trait multiple interval mapping (MTMIM) of QTL for inbred line crosses. We also develop a novel score-based method for estimating genome-wide significance level of putative QTL effects suitable for the MTMIM model. The MTMIM method is implemented in the freely available and widely used Windows QTL Cartographer software.
Throughout the paper, we provide compelling empirical evidences that: (1) the score-based threshold maintains proper type I error rate and tends to keep false discovery rate within an acceptable level; (2) the MTMIM method can deliver better parameter estimates and power than single trait multiple interval mapping method; (3) an analysis of Drosophila dataset illustrates how the MTMIM method can better extract information from datasets with measurements in multiple traits.
The MTMIM method represents a convenient statistical framework to test hypotheses of pleiotropic QTL versus closely linked nonpleiotropic QTL, QTL by environment interaction, and to estimate the total genotypic variance-covariance matrix between traits and to decompose it in terms of QTL-specific variance-covariance matrices, therefore, providing more details on the genetic architecture of complex traits.
尽管许多实验对多个性状进行了测量,但大多数研究使用单性状分析分别对每个性状进行数量性状基因座(QTL)定位分析。单性状分析没有利用性状之间可能存在的遗传和环境相关性。在本文中,我们提出了一种用于近交系杂交QTL的多性状多区间定位(MTMIM)的新统计方法。我们还开发了一种基于得分的新方法,用于估计适用于MTMIM模型的假定QTL效应的全基因组显著性水平。MTMIM方法在免费且广泛使用的Windows QTL Cartographer软件中实现。
在整篇论文中,我们提供了令人信服的实证证据表明:(1)基于得分的阈值保持了适当的I型错误率,并倾向于将错误发现率保持在可接受水平内;(2)MTMIM方法比单性状多区间定位方法能提供更好的参数估计和检验效能;(3)对果蝇数据集的分析说明了MTMIM方法如何能更好地从具有多个性状测量值的数据集中提取信息。
MTMIM方法代表了一个方便的统计框架,用于检验多效性QTL与紧密连锁的非多效性QTL、QTL与环境互作的假设,并估计性状之间的总基因型方差 - 协方差矩阵,并根据QTL特异性方差 - 协方差矩阵对其进行分解,因此,提供了关于复杂性状遗传结构的更多细节。