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

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 HSP90AA1 and NFATC1 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.

Ketersediaan

Informasi Detail

Judul Seri

JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION (JASA); Vol.117 No.540 December 2022

No. Panggil

-

Penerbit

: .,

Deskripsi Fisik

p. 1669-1683

Bahasa

English

ISBN/ISSN

-

Klasifikasi

NONE

Tipe Isi

-

Tipe Media

-

Tipe Pembawa

-

Edisi

-

Subjek

CLUSTERING
VARIABLE SELECTION
DIFFERENCE OF CONVEX
DNA METHYLATION
HIGH-DIMENSIONAL MEDIATORS
LINEAR STRUCTURAL EQUATION MODELING

Info Detail Spesifik

https://doi.org/10.1080/01621459.2022.2089572

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Fei Xue, Xiwei Tang, Grace Kim, Karestan C. Koenen, Chantel L. Martin, Sandro Galea, Derek Wildman, Monica Uddin, Annie Qu

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