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Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder.

ABSTRACT: AIM:Trauma exposure is a necessary, but not deterministic, contributor to post-traumatic stress disorder (PTSD). Epigenetic factors may distinguish between trauma-exposed individuals with versus without PTSD. MATERIALS & METHODS:We conducted a meta-analysis of PTSD epigenome-wide association studies in trauma-exposed cohorts drawn from civilian contexts. Whole blood-derived DNA methylation levels were analyzed in 545 study participants, drawn from the three civilian cohorts participating in the PTSD working group of the Psychiatric Genomics Consortium. RESULTS:Two CpG sites significantly associated with current PTSD in NRG1 (cg23637605) and in HGS (cg19577098). CONCLUSION:PTSD is associated with differential methylation, measured in blood, within HGS and NRG1 across three civilian cohorts.

SUBMITTER: Uddin M

PROVIDER: S-EPMC6331697 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder.

Uddin Monica M Ratanatharathorn Andrew A Armstrong Don D Kuan Pei-Fen PF Aiello Allison E AE Bromet Evelyn J EJ Galea Sandro S Koenen Karestan C KC Luft Benjamin B Ressler Kerry J KJ Wildman Derek E DE Nievergelt Caroline M CM Smith Alicia A

Epigenomics 20181120 12

<h4>Aim</h4>Trauma exposure is a necessary, but not deterministic, contributor to post-traumatic stress disorder (PTSD). Epigenetic factors may distinguish between trauma-exposed individuals with versus without PTSD.<h4>Materials & methods</h4>We conducted a meta-analysis of PTSD epigenome-wide association studies in trauma-exposed cohorts drawn from civilian contexts. Whole blood-derived DNA methylation levels were analyzed in 545 study participants, drawn from the three civilian cohorts partic ...[more]

PMID: 30456986

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Project description:The biological underpinnings of post-traumatic stress disorder (PTSD) have not been fully elucidated. Previous work suggests that alterations in the immune system are characteristic of the disorder. Identifying the biological mechanisms by which such alterations occur could provide fundamental insights into the etiology and treatment of PTSD. Here we identify specific epigenetic profiles underlying immune system changes associated with PTSD. Using blood samples (n=100) obtained from an ongoing, prospective epidemiologic study in Detroit, the Detroit Neighborhood Health Study (DNHS), we applied methylation microarrays to assay CpG sites from over 14,000 genes among 23 PTSD-affected and 77 PTSD-unaffected individuals. We show that immune system functions are significantly overrepresented among the annotations associated with genes uniquely unmethylated among those with PTSD. We further demonstrate that genes whose methylation levels are significantly and negatively correlated with traumatic burden show a similar strong signal of immune function among the PTSD-affected. The observed epigenetic variability in immune function by PTSD is corroborated using an independent biological marker of immune response to infection, cytomegalovirus—a typically latent herpesvirus whose activity was significantly higher among those with PTSD. These results provide the first report of peripheral epigenomic and CMV profiles associated with mental illness and suggest a new biological model of PTSD etiology in which an externally experienced traumatic event induces downstream alterations in immune function by reducing methylation levels of immune-related genes. Bisulfite conversion of whole blood-derived DNA samples was performed using the EZ-96 DNA methylation kit from Zymo Research. One microgram (μg) of each sample (including controls) was subjected to bisulfite conversion following manufacturer’s recommended protocol. 100 samples were analyzed of which 23 are PTSD affected and 77 are PTSD-unaffected. There were four technical replicates comprised of duplicate samples of two randomly selected individuals from the n=100 and duplicate samples of the control human methylated and unmethylated DNA.

Dataset Information

Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder.

Publications

Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder.

Similar Datasets

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