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Multiple-trait genome-wide association study based on principal component analysis for residual covariance matrix

机译:基于主成分分析的残基协方差矩阵多特征全基因组关联研究

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摘要

Given the drawbacks of implementing multivariate analysis for mapping multiple traits in genome-wide association study (GWAS), principal component analysis (PCA) has been widely used to generate independent ‘super traits' from the original multivariate phenotypic traits for the univariate analysis. However, parameter estimates in this framework may not be the same as those from the joint analysis of all traits, leading to spurious linkage results. In this paper, we propose to perform the PCA for residual covariance matrix instead of the phenotypical covariance matrix, based on which multiple traits are transformed to a group of pseudo principal components. The PCA for residual covariance matrix allows analyzing each pseudo principal component separately. In addition, all parameter estimates are equivalent to those obtained from the joint multivariate analysis under a linear transformation. However, a fast least absolute shrinkage and selection operator (LASSO) for estimating the sparse oversaturated genetic model greatly reduces the computational costs of this procedure. Extensive simulations show statistical and computational efficiencies of the proposed method. We illustrate this method in a GWAS for 20 slaughtering traits and meat quality traits in beef cattle.
机译:鉴于在全基因组关联研究(GWAS)中实施多变量分析来映射多个性状的弊端,主成分分析(PCA)已被广泛用于从原始多变量表型特征中产生独立的“超性状”,用于单变量分析。但是,此框架中的参数估计值可能与对所有特征进行联合分析得出的参数估计值不同,从而导致虚假的链接结果。在本文中,我们建议对残差协方差矩阵而不是表型协方差矩阵执行PCA,在此基础上将多个性状转换为一组伪主成分。残差协方差矩阵的PCA允许分别分析每个伪主成分。此外,所有参数估计值都等于从线性变换下的联合多元分析获得的参数估计值。但是,用于估计稀疏过饱和遗传模型的快速最小绝对收缩和选择算子(LASSO)大大降低了此过程的计算成本。大量的仿真显示了该方法的统计和计算效率。我们在GWAS中针对肉牛的20个屠宰性状和肉质性状说明了该方法。

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