An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci.
Date
2020-03
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Abstract
Background
Previous studies using candidate gene and genome-wide approaches have identified epigenetic changes in DNA methylation (DNAm) associated with posttraumatic stress disorder (PTSD).Methods
In this study, we performed an EWAS of PTSD in a cohort of Veterans (n = 378 lifetime PTSD cases and 135 controls) from the Translational Research Center for TBI and Stress Disorders (TRACTS) cohort assessed using the Illumina EPIC Methylation BeadChip which assesses DNAm at more than 850,000 sites throughout the genome. Our model included covariates for ancestry, cell heterogeneity, sex, age, and a smoking score based on DNAm at 39 smoking-associated CpGs. We also examined in EPIC-based DNAm data generated from pre-frontal cortex (PFC) tissue from the National PTSD Brain Bank (n = 72).Results
The analysis of blood samples yielded one genome-wide significant association with PTSD at cg19534438 in the gene G0S2 (p = 1.19 × 10-7, padj = 0.048). This association was replicated in an independent PGC-PTSD-EWAS consortium meta-analysis of military cohorts (p = 0.0024). We also observed association with the smoking-related locus cg05575921 in AHRR despite inclusion of a methylation-based smoking score covariate (p = 9.16 × 10-6), which replicates a previously observed PGC-PTSD-EWAS association (Smith et al. 2019), and yields evidence consistent with a smoking-independent effect. The top 100 EWAS loci were then examined in the PFC data. One of the blood-based PTSD loci, cg04130728 in CHST11, which was in the top 10 loci in blood, but which was not genome-wide significant, was significantly associated with PTSD in brain tissue (in blood p = 1.19 × 10-5, padj = 0.60, in brain, p = 0.00032 with the same direction of effect). Gene set enrichment analysis of the top 500 EWAS loci yielded several significant overlapping GO terms involved in pathogen response, including "Response to lipopolysaccharide" (p = 6.97 × 10-6, padj = 0.042).Conclusions
The cross replication observed in independent cohorts is evidence that DNA methylation in peripheral tissue can yield consistent and replicable PTSD associations, and our results also suggest that that some PTSD associations observed in peripheral tissue may mirror associations in the brain.Type
Department
Description
Provenance
Subjects
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Logue, Mark W, Mark W Miller, Erika J Wolf, Bertrand Russ Huber, Filomene G Morrison, Zhenwei Zhou, Yuanchao Zheng, Alicia K Smith, et al. (2020). An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci. Clinical epigenetics, 12(1). p. 46. 10.1186/s13148-020-0820-0 Retrieved from https://hdl.handle.net/10161/25893.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
Allison Elizabeth Ashley-Koch
My work focuses on the dissection of human traits using multi-omic technologies (genetics, epigenetics, metabolomics and proteomics). I am investigating the basis of several neurological and psychiatric conditions such as neural tube defects and post-traumatic stress disorder. I also study modifiers of sickle cell disease.
Jean Crowell Beckham
Interest in assessment and treatment of trauma, particularly as occurs for both women and men during military service; focus in treatment outcome of differential and collective contribution for psychopharmacological and behavioral interventions in PTSD populations; long term physical health effects of chronic posttraumatic stress disorder.
Gerald Arthur Grant
Nathan Andrew Kimbrel
My primary areas of interest include the etiology, assessment, and treatment of PTSD, depression, suicide, and non-suicidal self-injury. I primarily work with veterans, firefighters, and emergency medical personnel due to their high levels of occupational exposure to traumatic stress. I also have long-standing interests in genetics, epigenetics, GxE research, personality, smoking, comorbidity, and statistical modeling procedures, such as CFA, SEM, and mixture modeling.
Christine Elizabeth Marx
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.