Cell-type-specific and inflammatory DNA methylation patterns associated with PTSD
Brain Behavior and Immunity, vol. 128, pp. 540–548
Abstract
BACKGROUND: Epigenetic modifications, including DNA methylation (DNAm), can change in response to traumatic stress exposure, and may help to distinguish between individuals with and without PTSD. Here, we examine the DNAm patterns specific to immune cell types and inflammation in those with PTSD. METHODS: This study includes 3,277 participants from 11 cohorts participating in the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup. DNAm was assayed from blood with the MethylationEPIC BeadChip. A standardized QC pipeline was applied and used to impute cell composition. Within each cohort, we identified cell-type-specific DNAm patterns associated with PTSD, controlling for sex (if applicable), age, and ancestry. Meta-analyses were performed from summary statistics. RESULTS: PTSD cases had lower proportions of B cells and NK cells as well as higher proportions of neutrophils when compared to trauma-exposed controls. Overall, we identified 96 PTSD-associated CpGs across six types of immune cells. Most of these differences were identified in B cells, with 95 % exhibiting lower methylation levels in those with PTSD. Interestingly, the PTSD-associated CpGs annotated to a gene in B cells were enriched in a recent GWAS of PTSD (p < 0.0001). CONCLUSIONS: This study identifies novel PTSD-associated CpGs in individual immune cell types and supports the role of immune dysregulation and inflammation in PTSD.
Authors 49
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Affiliation as printed
Emory University, Department of Gynecology and Obstetrics, Atlanta, GA, USA; Emory University, Department of Human Genetics, Atlanta, GA, USA; Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA. Electronic address: alicia.smith@emory.edu
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Affiliation as printed
Emory University, Department of Gynecology and Obstetrics, Atlanta, GA, USA
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University of California San Diego · VA San Diego Healthcare System · Center of Excellence for Stress and Mental Health
Affiliation as printed
University of California San Diego, Department of Psychiatry, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA; Veterans Affairs San Diego Healthcare System, Research Service, San Diego, CA, USA
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Affiliation as printed
Columbia University, Robert N Butler Columbia Aging Center, Department of Epidemiology, New York, NY, USA
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University of California San Diego
Affiliation as printed
University of California San Diego, Department of Psychiatry, La Jolla, CA, USA
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University Medical Center Utrecht · Dimence · Amsterdam University Medical Centers
Affiliation as printed
Amsterdam UMC, Department of Psychiatry, Amsterdam, NH, Netherland; Dimence Specialised Mental Health, Mood Disorders, Deventer, OV, Netherland; University Medical Center Utrecht, Department Psychiatry, Utrecht, UT, Netherland
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Affiliation as printed
Alpert Medical School of Brown University, Department of Psychiatry and Human Behavior, Providence, RI, USA
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Affiliation as printed
Biogen Inc., Translational Medicine, Cambridge, MA, USA
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Affiliation as printed
University of Cape Town, Division of Human Genetics, Cape Town, Western Province, South Africa
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Affiliation as printed
Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA
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Harvard University · VA Boston Healthcare System
Affiliation as printed
Harvard Medical School, Department of Psychiatry, Boston, MA, USA; VA Boston Healthcare System, Geriatric Research, Education and Clinical Center (GRECC), Boston, MA, USA; VA Boston Healthcare System, Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS), Boston, MA, USA
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Yale University · VA Connecticut Healthcare System
Affiliation as printed
VA Connecticut Healthcare Center, Psychiatry Service, West Haven, CT, USA; Yale University School of Medicine, Departments of Psychiatry, Genetics and Neuroscience, New Haven, CT, USA
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Affiliation as printed
Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA
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Affiliation as printed
The Ohio State University, Department of Psychology, Columbus, OH, USA
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University of California San Diego · Center of Excellence for Stress and Mental Health
Affiliation as printed
University of California San Diego, Department of Psychiatry, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA; University of California San Diego, Herbert Wertheim School of Public Health and Human Longevity Science, La Jolla, CA, USA
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Affiliation as printed
Harvard Medical School, Department of Health Care Policy, Boston, MA, USA
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Affiliation as printed
The Ohio State University, College of Medicine, Institute for Behavioral Medicine Research, Columbus, OH, USA; The Ohio State University, College of Medicine, Psychiatry & Behavioral Health, Columbus, OH, USA
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South African Medical Research Council · University of Cape Town
Affiliation as printed
University of Cape Town, Department of Psychiatry & Mental Health, Cape Town, Western Province, South Africa; University of Cape Town, Neuroscience Institute, Cape Town, Western Province, South Africa; University of Cape Town, SA MRC Unit on Risk & Resilience in Mental Disorders, Cape Town, Western Province, South Africa
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Broad Institute · Harvard University · Massachusetts General Hospital · Stanley Center for Psychiatric Research · Massachusetts Institute of Technology
Affiliation as printed
Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA; Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, MA, USA; Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Boston, MA, USA
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Affiliation as printed
Texas A&M University College of Medicine, Department of Psychiatry and Behavioral Sciences, Bryan, TX, USA
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University of North Carolina at Chapel Hill
Affiliation as printed
University of North Carolina at Chapel Hill, Department of Anesthesiology, Chapel Hill, NC, USA; University of North Carolina at Chapel Hill, Institute for Trauma Recovery, Chapel Hill, NC, USA
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University of North Carolina at Chapel Hill
Affiliation as printed
University of North Carolina at Chapel Hill, Institute for Trauma Recovery, Chapel Hill, NC, USA; University of North Carolina at Chapel Hill, Department of Psychiatry, Chapel Hill, NC, USA
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Affiliation as printed
Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA
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Harvard University · VA Boston Healthcare System
Affiliation as printed
Harvard Medical School, Department of Psychiatry, Boston, MA, USA; VA Boston Healthcare System, Geriatric Research, Education and Clinical Center (GRECC), Boston, MA, USA; VA Boston Healthcare System, Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS), Boston, MA, USA
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Boston University · VA Boston Healthcare System · National Center for Post Traumatic Stress Disorder
Affiliation as printed
Boston University Chobanian & Avedisian School of Medicine, Department of Psychiatry, Boston, MA, USA; VA Boston Healthcare System, National Center for PTSD, Boston, MA, USA
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Affiliation as printed
University of Cape Town, Department of Psychiatry and Mental Health, Cape Town, Western Province, South Africa
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Affiliation as printed
Alpert Brown Medical School, Department of Emergency Medicine, Providence, RI, USA; Alpert Brown Medical School, Department of Pediatrics, Providence, RI, USA; Alpert Brown Medical School, Department of Psychiatry and Human Behavior, Providence, RI, USA
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Affiliation as printed
Northern Illinois University, Department of Psychology, DeKalb, IL, USA
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Affiliation as printed
Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA
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Emory University · Atlanta VA Health Care System · Atlanta VA Medical Center
Affiliation as printed
Emory University School of Medicine, Department of Psychiatry & Behavioral Sciences, Atlanta, GA, USA; Joseph Maxwell Cleland Atlanta Veterans Affairs Healthcare System, Mental Health Service Line, Atlanta, GA, USA
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Harvard University · Emory University · McLean Hospital
Affiliation as printed
Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA; Harvard Medical School, Department of Psychiatry, Boston, MA, USA; McLean Hospital, Division of Depression and Anxiety, Belmont, MA, USA
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University of California San Diego · VA San Diego Healthcare System · Center of Excellence for Stress and Mental Health
Affiliation as printed
University of California San Diego, Department of Psychiatry, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA; Veterans Affairs San Diego Healthcare System, Research Service, San Diego, CA, USA
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Broad Institute · Harvard University · Maastricht University · Stanley Center for Psychiatric Research · Massachusetts Institute of Technology
Affiliation as printed
Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA; Maastricht University, Department of Psychiatry and Neuropsychology, Maastricht, Limburg, Netherland
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Broad Institute · Harvard University · Massachusetts General Hospital · Stanley Center for Psychiatric Research · Massachusetts Institute of Technology
Affiliation as printed
Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA; Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Boston, MA, USA; Massachusetts General Hospital, Department of Psychiatry, Boston, MA, USA
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South African Medical Research Council · University of Cape Town
Affiliation as printed
University of Cape Town, Department of Psychiatry & Mental Health, Cape Town, Western Province, South Africa; University of Cape Town, Neuroscience Institute, Cape Town, Western Province, South Africa; University of Cape Town, SA MRC Unit on Risk & Resilience in Mental Disorders, Cape Town, Western Province, South Africa
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University of California San Diego · VA San Diego Healthcare System
Affiliation as printed
University of California San Diego, Department of Psychiatry, La Jolla, CA, USA; University of California San Diego, School of Public Health, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, Psychiatry Service, San Diego, CA, USA
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Uniformed Services University of the Health Sciences
Affiliation as printed
Uniformed Services University of Health Sciences, Center for the Study of Traumatic Stress, Department of Psychiatry, Bethesda, MD, USA
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Boston University · VA Boston Healthcare System
Affiliation as printed
Boston University School of Medicine, Department of Psychiatry, Boston, MA, USA; VA Boston Healthcare System, Memory Disorders Research Center, Boston, MA, USA
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Eric H. G. J. M. Vermetten Aachen
Leiden University Medical Center · New York University
Affiliation as printed
Leiden University Medical Center, Department of Psychiatry, Leiden, ZH, Netherland; New York University School of Medicine, Department of Psychiatry, New York, NY, USA
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Amsterdam Neuroscience · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Amsterdam, NH, Netherland; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam, Holland, Netherland; Amsterdam University Medical Center, Amsterdam Neuroscience Research Institute, Mood, Anxiety, Psychosis, Stress & Sleep Program, Amsterdam, NH, Netherland
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Affiliation as printed
University of South Florida College of Public Health, Genomics Program, Tampa, FL, USA
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Affiliation as printed
University of Michigan, Survey Research Center, Ann Arbor, MI, USA
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Affiliation as printed
Boston University Chobanian & Avedisian School of Medicine, Department of Biomedical Genetics, Boston, MA, USA
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Boston University · VA Boston Healthcare System · National Center for Post Traumatic Stress Disorder
Affiliation as printed
Boston University Chobanian & Avedisian School of Medicine, Department of Psychiatry, Boston, MA, USA; VA Boston Healthcare System, National Center for PTSD, Boston, MA, USA
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University of North Carolina at Chapel Hill
Affiliation as printed
University of North Carolina at Chapel Hill, Department of Anesthesiology, Chapel Hill, NC, USA; University of North Carolina at Chapel Hill, Institute for Trauma Recovery, Chapel Hill, NC, USA
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Boston University · University of North Carolina at Chapel Hill · VA Boston Healthcare System · National Center for Post Traumatic Stress Disorder
Affiliation as printed
Boston University Chobanian & Avedisian School of Medicine, Department of Psychiatry, Boston, MA, USA; VA Boston Healthcare System, National Center for PTSD, Boston, MA, USA; Boston University School of Public Health, Department of Biostatistics, Boston, MA, USA; University of North Carolina at Chapel Hill, Carolina Stress Initiative, Chapel Hill, NC, USA
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University of California San Diego · VA San Diego Healthcare System · Center of Excellence for Stress and Mental Health
Affiliation as printed
University of California San Diego, Department of Psychiatry, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA; Veterans Affairs San Diego Healthcare System, Research Service, San Diego, CA, USA
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Affiliation as printed
University of South Florida College of Public Health, Genomics Program, Tampa, FL, USA
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University of North Carolina at Chapel Hill
Affiliation as printed
University of North Carolina at Chapel Hill, Institute for Trauma Recovery, Chapel Hill, NC, USA; University of North Carolina at Chapel Hill, Department of Psychiatry, Chapel Hill, NC, USA; University of North Carolina at Chapel Hill, Carolina Stress Initiative, Chapel Hill, NC, USA; University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, NC, USA
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