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Mixed Linear Model Approaches of Association Mapping for Complex Traits Based on Omics Variants

机译:基于组学变异的复杂性状关联映射的混合线性模型方法

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摘要

Precise prediction for genetic architecture of complex traits is impeded by the limited understanding on genetic effects of complex traits, especially on gene-by-gene (GxG) and gene-by-environment (GxE) interaction. In the past decades, an explosion of high throughput technologies enables omics studies at multiple levels (such as genomics, transcriptomics, proteomics, and metabolomics). The analyses of large omics data, especially two-loci interaction analysis, are very time intensive. Integrating the diverse omics data and environmental effects in the analyses also remain challenges. We proposed mixed linear model approaches using GPU (Graphic Processing Unit) computation to simultaneously dissect various genetic effects. Analyses can be performed for estimating genetic main effects, GxG epistasis effects, and GxE environment interaction effects on large-scale omics data for complex traits, and for estimating heritability of specific genetic effects. Both mouse data analyses and Monte Carlo simulations demonstrated that genetic effects and environment interaction effects could be unbiasedly estimated with high statistical power by using the proposed approaches.
机译:对复杂性状遗传结构的精确预测受到对复杂性状遗传效应的了解的限制,尤其是对基因间基因(GxG)和基因间环境(GxE)相互作用的了解有限。在过去的几十年中,高通量技术的爆炸式增长使得能够在多个层次上进行组学研究(例如基因组学,转录组学,蛋白质组学和代谢组学)。大型组学数据的分析,尤其是两轨相互作用分析,非常耗时。在分析中整合各种组学数据和环境影响也仍然是挑战。我们提出了使用GPU(图形处理单元)计算来同时剖析各种遗传效应的混合线性模型方法。可以进行分析以估计复杂特征的大规模组学数据的遗传主要效应,GxG上位效应和GxE环境相互作用效应,以及评估特定遗传效应的遗传力。鼠标数据分析和蒙特卡洛模拟都表明,通过使用所提出的方法,遗传效应和环境相互作用效应可以以较高的统计能力无偏估计。

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