Multikernel linear mixed model with adaptive lasso for complex phenotype prediction.

Multikernel linear mixed model with adaptive lasso for complex phenotype prediction.
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DOI:
10.1002/sim.8477
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发表时间:
2020-04-30
影响因子:
2
通讯作者:
Lu Q
Lu Q
中科院分区:
医学3区
文献类型:
--
作者:
Wen Y;Lu Q

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线性混合模型(Linear mixed models,LMRM)及其扩展已被广泛应用于高维基因组数据分析。虽然LIGHTN在风险预测研究中有很大的前景,但数据的高维性和基因组区域的不同效应大小带来了巨大的分析和计算挑战。在这项工作中,我们提出了一个多核线性混合模型与自适应套索(KLMM-AL)预测表型使用高维基因组数据。我们开发了两种算法来估计我们的模型的参数,也建立了渐近性质的LMM与自适应套索时,只有一个相关的观察。建议的KLMM-AL可以考虑来自不同基因组区域的异质效应大小,捕获加性和非加性遗传效应,并自适应地和有效地选择预测基因组区域及其相应的影响。通过仿真研究,我们证明了KLMM-AL优于大多数现有的方法。此外,KLMM-AL实现了选择预测基因组区域的高灵敏度和特异性。KLMM-AL进一步说明了从阿尔茨海默病神经影像学倡议获得的测序数据集的应用程序。
Linear mixed models (LMMs) and their extensions have been widely used for high-dimensional genomic data analyses. While LMMs hold great promise for risk prediction research, the high dimensionality of the data and different effect sizes of genomic regions bring great analytical and computational challenges. In this work, we present a multikernel linear mixed model with adaptive lasso (KLMM-AL) to predict phenotypes using high-dimensional genomic data. We develop two algorithms for estimating parameters from our model and also establish the asymptotic properties of LMM with adaptive lasso when only one dependent observation is available. The proposed KLMM-AL can account for heterogeneous effect sizes from different genomic regions, capture both additive and nonadditive genetic effects, and adaptively and efficiently select predictive genomic regions and their corresponding effects. Through simulation studies, we demonstrate that KLMM-AL outperforms most of existing methods. Moreover, KLMM-AL achieves high sensitivity and specificity of selecting predictive genomic regions. KLMM-AL is further illustrated by an application to the sequencing dataset obtained from the Alzheimer’s disease neuroimaging initiative.
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