论文标题

贝叶斯分层模型用于高维中介分析,并协调相关介体的选择

Bayesian Hierarchical Models for High-Dimensional Mediation Analysis with Coordinated Selection of Correlated Mediators

论文作者

Song, Yanyi, Zhou, Xiang, Kang, Jian, Aung, Max T., Zhang, Min, Zhao, Wei, Needham, Belinda L., Kardia, Sharon L. R., Liu, Yongmei, Meeker, John D., Smith, Jennifer A., Mukherjee, Bhramar

论文摘要

我们考虑贝叶斯高维中介分析,以识别大量相关的潜在介体中介导从暴露变量到感兴趣结果的活性介质。在现代数据分析中通常观察到介体之间的相关性;示例包括大脑图像数据中连接区域内的激活体素,基因组数据中基因网络驱动的调节信号以及来自同一来源的相关暴露数据。当主动介体之间存在相关性时,无法解释这种相关性的调解分析可能是最佳的,并且可能导致识别活性介体的损失。在最近的高维中介分析框架的基础上,我们提出了两个贝叶斯分层模型,一种具有高斯混合物,这使得相关的介体选择,另一个具有POTTS混合物,这说明了活性介体之间在中介分析中的相关性。我们为这两种方法开发有效的采样算法。各种模拟表明,我们的方法能够有效地识别相关的主动介体,这可以通过使用现有的现有方法在主动介体之间具有先前独立性而丢失。所提出的方法应用于生命码出生队列和动脉粥样硬化(MESA)的多种族研究,并确定具有重要生物学意义的新活性介质。

We consider Bayesian high-dimensional mediation analysis to identify among a large set of correlated potential mediators the active ones that mediate the effect from an exposure variable to an outcome of interest. Correlations among mediators are commonly observed in modern data analysis; examples include the activated voxels within connected regions in brain image data, regulatory signals driven by gene networks in genome data and correlated exposure data from the same source. When correlations are present among active mediators, mediation analysis that fails to account for such correlation can be sub-optimal and may lead to a loss of power in identifying active mediators. Building upon a recent high-dimensional mediation analysis framework, we propose two Bayesian hierarchical models, one with a Gaussian mixture prior that enables correlated mediator selection and the other with a Potts mixture prior that accounts for the correlation among active mediators in mediation analysis. We develop efficient sampling algorithms for both methods. Various simulations demonstrate that our methods enable effective identification of correlated active mediators, which could be missed by using existing methods that assume prior independence among active mediators. The proposed methods are applied to the LIFECODES birth cohort and the Multi-Ethnic Study of Atherosclerosis (MESA) and identified new active mediators with important biological implications.

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