Heterogeneous Mediation Analysis on Epigenomic PTSD and Traumatic Stress in a Predominantly African American Cohort
Heterogeneous Mediation Analysis on Epigenomic PTSD and Traumatic Stress in a Predominantly African American Cohort
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DOI：
10.1080/01621459.2022.2089572
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发表时间：
2022-07-08
影响因子：
3.7
通讯作者：
Qu，Annie
中科院分区：
文献类型：
--
作者：
Xue，Fei;Tang，Xiwei;Qu，Annie
DNA甲基化（DNAm）通过介导创伤与创伤后应激障碍（PTSD）之间的关系，在PTSD中起着重要作用。然而，非裔美国人PTSD的潜在机制仍然未知。为了填补这一空白，在这篇文章中，我们调查了DNA如何介导创伤经历对底特律社区健康研究（DNHS）（2008-2013）中PTSD症状的影响，该研究主要涉及非洲裔美国人。为了实现这一目标，我们开发了一种新的调解分析方法，高维潜在的DNAm调解员。我们的方法的一个关键的新奇是，我们认为异质性的中介效应在亚群。具体而言，不同亚群中的介质可能对结果产生相反的影响，因此在传统的同质模型框架下可能难以识别。相比之下，所提出的方法可以估计异质中介效应，并确定子群体中的个人共享类似的效果。仿真研究表明，所提出的方法优于现有的方法，同质和异构数据。我们还介绍了我们的调解分析结果的数据集与125名参与者和超过CpG位点的DNHS研究。所提出的方法发现三个亚组的主题，并确定相应的基因，如HSP 90 AA 1和NFATC 1已被链接到PTSD症状的文献中的DNAm介质。我们的发现可能有助于未来PTSD机制的更细粒度研究和PTSD新治疗方法的开发。本文的补充材料可在网上查阅。
DNA methylation (DNAm) has been suggested to play a critical role in post-traumatic stress disorder (PTSD), through mediating the relationship between trauma and PTSD. However, this underlying mechanism of PTSD for African Americans still remains unknown. To fill this gap, in this article, we investigate how DNAm mediates the effects of traumatic experiences on PTSD symptoms in the Detroit Neighborhood Health Study (DNHS) (2008–2013) which involves primarily African Americans adults. To achieve this, we develop a new mediation analysis approach for high-dimensional potential DNAm mediators. A key novelty of our method is that we consider heterogeneity in mediation effects across subpopulations. Specifically, mediators in different subpopulations could have opposite effects on the outcome, and thus could be difficult to identify under a traditional homogeneous model framework. In contrast, the proposed method can estimate heterogeneous mediation effects and identifies subpopulations in which individuals share similar effects. Simulation studies demonstrate that the proposed method outperforms existing methods for both homogeneous and heterogeneous data. We also present our mediation analysis results of a dataset with 125 participants and more thanCpG sites from the DNHS study. The proposed method finds three subgroups of subjects and identifies DNAm mediators corresponding to genes such asHSP90AA1andNFATC1which have been linked to PTSD symptoms in literature. Our finding could be useful in future finer-grained investigation of PTSD mechanism and in the development of new treatments for PTSD. Supplementary materials for this article are available online.