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全基因组关联图谱中一元和多元混合效应模型的t检验比较。

Comparison of -tests for Univariate and Multivariate Mixed-Effect Models in Genome-Wide Association Mapping.

作者信息

Onogi Akio

机构信息

Institute of Crop Science, National Agriculture and Food Research Organization, Tsukuba, Japan.

Japan Science and Technology Agency PRESTO, Kawaguchi, Japan.

出版信息

Front Genet. 2019 Feb 4;10:30. doi: 10.3389/fgene.2019.00030. eCollection 2019.

Abstract

Genome-wide association mapping (GWA) has been widely applied to a variety of species to identify genomic regions responsible for quantitative traits. The use of multivariate information could enhance the detection power of GWA. Although mixed-effect models are frequently used for GWA, the utility of -tests for multivariate mixed-effect models is not well-recognized. Thus, we compared the -tests for univariate and multivariate mixed-effect models with simulations. The superiority of the multivariate -test over the univariate test varied depending on three parameters: phenotypic correlation between variates (), relative size of quantitative trait locus effects between variates ( ), and missing proportion of phenotypic records ( ). Simulation results showed that, when was low, the multivariate -test outperformed the univariate test as and differ, and as increased, the multivariate -test outperformed as increased. These observations were consistent with results of the analytical evaluation of the -value. When was at the maximum, i.e., when no individual had phenotypic values for multiple variates, as in the case of meta-analysis, the multivariate -test gained more detection power as increased. Although using multivariate information in mixed-effect model contexts did not always ensure more detection power than with univariate tests, the multivariate -test will be a method applied when multivariate data are available because it does not show inflation of signals and could lead to new findings.

摘要

全基因组关联定位(GWA)已被广泛应用于多种物种,以识别负责数量性状的基因组区域。使用多变量信息可以提高GWA的检测能力。虽然混合效应模型经常用于GWA,但多变量混合效应模型的t检验的效用尚未得到充分认识。因此,我们通过模拟比较了单变量和多变量混合效应模型的t检验。多变量t检验相对于单变量检验的优越性取决于三个参数:变量之间的表型相关性(ρ)、变量之间数量性状位点效应的相对大小(γ)以及表型记录的缺失比例(m)。模拟结果表明,当ρ较低时,随着γ和m不同,多变量t检验优于单变量检验,并且随着m增加,多变量t检验随着γ增加而表现更优。这些观察结果与t值的分析评估结果一致。当ρ处于最大值时,即当没有个体具有多个变量的表型值时,如在荟萃分析的情况下,随着γ增加,多变量t检验获得更多的检测能力。虽然在混合效应模型背景下使用多变量信息并不总是确保比单变量检验具有更多的检测能力,但多变量t检验将是一种在有多变量数据时应用的方法,因为它不会显示信号膨胀并且可能会带来新的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c0/6369166/734fafc5ea93/fgene-10-00030-g0001.jpg

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