Heterogeneous Mediation Analysis on Epigenomic PTSD and Traumatic Stress in a Predominantly African American Cohort

• 成果类型: Article
• 署名作者: Xue, Fei; Tang, Xiwei; Kim, Grace; Koenen, Karestan C.; Martin, Chantel L.; Galea, Sandro; Wildman, Derek; Uddin, Monica; Qu, Annie
• 署名单位: Purdue University System; Purdue University; University of Virginia; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; Harvard University; Harvard T.H. Chan School of Public Health; University of North Carolina; University of North Carolina Chapel Hill; Boston University; State University System of Florida; University of South Florida; University of California System; University of California Irvine
• 刊物名称: JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
• ISSN/ISSBN: 0162-1459
• DOI: 10.1080/01621459.2022.2089572
• 发表日期: 2022
• 页码: 1669-1683
• 关键词: glucocorticoid-receptor gene; posttraumatic-stress; depressive symptoms; dna methylation; variable selection; disorder; association; exposure; RISK; likelihood

摘要

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 than 450,000 CpG sites from the DNHS study. The proposed method finds three subgroups of subjects and identifies DNAm mediators corresponding to genes such as HSP9OAA1 and NFATCI which 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.