Sztepanacz Jacqueline L, Blows Mark W
School of Biological Sciences, University of Queensland, St. Lucia, Queensland, Australia 4072
School of Biological Sciences, University of Queensland, St. Lucia, Queensland, Australia 4072.
Genetics. 2017 Jul;206(3):1271-1284. doi: 10.1534/genetics.116.198606. Epub 2017 May 5.
The distribution of genetic variance in multivariate phenotypes is characterized by the empirical spectral distribution of the eigenvalues of the genetic covariance matrix. Empirical estimates of genetic eigenvalues from random effects linear models are known to be overdispersed by sampling error, where large eigenvalues are biased upward, and small eigenvalues are biased downward. The overdispersion of the leading eigenvalues of sample covariance matrices have been demonstrated to conform to the Tracy-Widom (TW) distribution. Here we show that genetic eigenvalues estimated using restricted maximum likelihood (REML) in a multivariate random effects model with an unconstrained genetic covariance structure will also conform to the TW distribution after empirical scaling and centering. However, where estimation procedures using either REML or MCMC impose boundary constraints, the resulting genetic eigenvalues tend not be TW distributed. We show how using confidence intervals from sampling distributions of genetic eigenvalues without reference to the TW distribution is insufficient protection against mistaking sampling error as genetic variance, particularly when eigenvalues are small. By scaling such sampling distributions to the appropriate TW distribution, the critical value of the TW statistic can be used to determine if the magnitude of a genetic eigenvalue exceeds the sampling error for each eigenvalue in the spectral distribution of a given genetic covariance matrix.
多变量表型中遗传方差的分布由遗传协方差矩阵特征值的经验谱分布来表征。已知随机效应线性模型中遗传特征值的经验估计会因抽样误差而过度离散,其中大特征值向上偏倚,小特征值向下偏倚。样本协方差矩阵主导特征值的过度离散已被证明符合特雷西 - 威多姆(TW)分布。在此我们表明,在具有无约束遗传协方差结构的多变量随机效应模型中,使用限制最大似然法(REML)估计的遗传特征值在经验缩放和中心化后也将符合TW分布。然而,在使用REML或MCMC的估计程序施加边界约束的情况下,所得的遗传特征值往往不呈TW分布。我们展示了仅使用遗传特征值抽样分布的置信区间而不参考TW分布,不足以防止将抽样误差误判为遗传方差,特别是当特征值较小时。通过将此类抽样分布缩放到适当的TW分布,TW统计量的临界值可用于确定给定遗传协方差矩阵谱分布中每个遗传特征值的大小是否超过抽样误差。
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