PTSD is associated with increased DNA methylation across regions of HLA-DPB1 and SPATC1L

Katrinli, Şeyma; Zheng, Yuanchao; Gautam, Aarti; Hammamieh, Rasha; Yang, Ruoting; Venkateswaran, Suresh; Kilaru, Varun; Lori, Adriana; Hinrichs, Rebecca; Powers, Abigail; Gillespie, Charles F.; Wingo, Aliza P.; Michopoulos, Vasiliki; Jovanović, Tanja; Wolf, Erika J.; McGlinchey, Regina E.; Milberg, William; Kugathasan, Subra; Jett, Marti; Logue, Mark W.; Ressler, Kerry J.; Smith, Alicia K.

doi:10.1016/j.bbi.2020.10.023

Cited by 21 publications

(10 citation statements)

References 73 publications

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“…In addition to the protective effect of HLA-A*02:01, we also documented protective effects of DPB1*04:01 on lifetime PTSD. Although ours is the first study to document an association of this specific allele with PTSD to our knowledge, one study found that PTSD is associated with increased DPB1 methylation in African Americans, and decreased DPB1 methylation in Caucasians ( Katrinli et al, 2021 ), and DPB1*04:01 has been shown to exert protective effects against autoimmune disorders and conditions affecting the brain ( Hadley et al, 2015 ; Kasai et al, 2022 ; Ollila et al, 2015 ; Watanabe et al, 2021 ). In addition to confirming previously identified risk of DPB1*17:01 on PTSD, we documented other alleles with even more robust evidence of susceptibility to PTSD ( Table 2 ).…”

Section: Discussionmentioning

confidence: 74%

“…Variation in the HLA region, the most highly polymorphic region of the human genome ( Trowsdale and Knight, 2013 ), has been shown to contribute to disease susceptibility ( Dendrou et al, 2018 ), including some evidence implicating HLA in PTSD. An initial genome-wide association study (GWAS) identified the HLA-B locus as relevant to PTSD in African American males ( Nievergelt et al, 2018 ), and DNA methylation in the HLA region has been associated with post-deployment PTSD status in male veterans of European American ancestry ( Snijders et al, 2020 ) and in African American women ( Katrinli et al, 2021 ). To our knowledge, only one prior study has investigated the influence of specific HLA alleles, imputed from GWAS, on PTSD.…”

Section: Introductionmentioning

confidence: 99%

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Immunogenetics of posttraumatic stress disorder (PTSD) in women veterans

James¹,

Georgopoulos²

2022

Brain, Behavior, & Immunity - Health

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Immunogenetics of posttraumatic stress disorder (PTSD) in women veterans

James¹,

Georgopoulos²

2022

Brain, Behavior, & Immunity - Health

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“…A longitudinal meta-analysis of three male military cohorts reported that methylation levels across HLA-DPB1 and HLA-DRB1 regions are lower after deployment in individuals with PTSD ( Snijders et al, 2020 ). However, a recent study reported that PTSD was associated with increased methylation across HLA-DPB1 in a civilian cohort of predominantly African American women, whilst the association between PTSD and HLA-DPB1 methylation was in opposite direction in a military cohort of predominantly Caucasian males ( Katrinli et al, 2021 ). The difference in this direction of association may be explained by sequence-dependent DNA methylation patterns that are ancestry-specific, as the region includes methylation quantitative trait loci (meQTLs) that differ in minor allele frequencies (MAFs) by more than 40% between those of African versus European decent.…”

Section: Human Leukocyte Antigen (Hla) and Ptsdmentioning

confidence: 96%

Immune system regulation and role of the human leukocyte antigen in posttraumatic stress disorder

Katrinli

Smith

2021

Neurobiology of Stress

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Posttraumatic stress disorder (PTSD) is a debilitating condition that adversely affect mental and physical health. Recent studies have increasingly explored the role of the immune system in risk for PTSD and its related symptoms. Dysregulation of the immune system may lead to central nervous system tissue damage and impair learning and memory processes. Individuals with PTSD often have comorbid inflammatory or auto-immune disorders. Evidence shows associations between PTSD and multiple genes that are involved in immune-related or inflammatory pathways. In this review, we will summarize the evidence of immune dysregulation in PTSD, outlining the contributions of distinct cell types, genes, and biological pathways. We use the Human Leukocyte Antigen (HLA) locus to illustrate the contribution of genetic variation to function in different tissues that contribute to PTSD etiology, severity, and comorbidities.

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“…Nevertheless, support for links between trauma, PTSD, and inflammation has been observed across omics studies. For example, hypothesis-free genetic, epigenetic, and gene expression studies of PTSD have identified genes related to the immune system [e.g., genes in the HLA region and those encoding inflammatory cytokines (IL-8, IL-16)] [ 84 – 86 ], which parallels work with candidate genes [ 65 ]. Additionally, some studies have found that variation in and/or methylation of immune-relevant genes underlie associations of PTSD and inflammation.…”

Section: Biological Mechanisms Linking Trauma With Cvd Riskmentioning

confidence: 99%

Psychological and biological mechanisms linking trauma with cardiovascular disease risk

et al. 2023

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Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and experiences of psychological trauma have been associated with subsequent CVD onset. Identifying key pathways connecting trauma with CVD has the potential to inform more targeted screening and intervention efforts to offset elevated cardiovascular risk. In this narrative review, we summarize the evidence for key psychological and biological mechanisms linking experiences of trauma with CVD risk. Additionally, we describe various methodologies for measuring these mechanisms in an effort to inform future research related to potential pathways. With regard to mechanisms involving posttraumatic psychopathology, the vast majority of research on psychological distress after trauma and CVD has focused on posttraumatic stress disorder (PTSD), even though posttraumatic psychopathology can manifest in other ways as well. Substantial evidence suggests that PTSD predicts the onset of a range of cardiovascular outcomes in trauma-exposed men and women, yet more research is needed to better understand posttraumatic psychopathology more comprehensively and how it may relate to CVD. Further, dysregulation of numerous biological systems may occur after trauma and in the presence of posttraumatic psychopathology; these processes of immune system dysregulation and elevated inflammation, oxidative stress, mitochondrial dysfunction, renin-angiotensin system dysregulation, and accelerated biological aging may all contribute to subsequent cardiovascular risk, although more research on these pathways in the context of traumatic stress is needed. Given that many of these mechanisms are closely intertwined, future research using a systems biology approach may prove fruitful for elucidating how processes unfold to contribute to CVD after trauma.

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PTSD is associated with increased DNA methylation across regions of HLA-DPB1 and SPATC1L

Cited by 21 publications

References 73 publications

Immunogenetics of posttraumatic stress disorder (PTSD) in women veterans

Immunogenetics of posttraumatic stress disorder (PTSD) in women veterans

Immune system regulation and role of the human leukocyte antigen in posttraumatic stress disorder

Psychological and biological mechanisms linking trauma with cardiovascular disease risk

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