Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR

被引：0

作者：

Alicia K. Smith

Andrew Ratanatharathorn

Adam X. Maihofer

Robert K. Naviaux

Allison E. Aiello

Ananda B. Amstadter

Allison E. Ashley-Koch

Dewleen G. Baker

Jean C. Beckham

Marco P. Boks

Evelyn Bromet

Michelle Dennis

Sandro Galea

Melanie E. Garrett

Elbert Geuze

Guia Guffanti

Michael A. Hauser

Seyma Katrinli

Varun Kilaru

Ronald C. Kessler

Nathan A. Kimbrel

Karestan C. Koenen

Pei-Fen Kuan

Kefeng Li

Mark W. Logue

Adriana Lori

Benjamin J. Luft

Mark W. Miller

Jane C. Naviaux

Nicole R. Nugent

Xuejun Qin

Kerry J. Ressler

Victoria B. Risbrough

Bart P. F. Rutten

Murray B. Stein

Robert J. Ursano

Eric Vermetten

Christiaan H. Vinkers

Lin Wang

Nagy A. Youssef

Monica Uddin

Caroline M. Nievergelt

机构：

[1] Emory University,Duke Molecular Physiology Institute

[2] Department of Gynecology and Obstetrics,Department of Neurosurgery

[3] Emory University,Department of Psychiatry

[4] Department of Psychiatry & Behavioral Sciences,undefined

[5] Columbia University,undefined

[6] Department of Epidemiology,undefined

[7] University of California San Diego,undefined

[8] Department of Psychiatry,undefined

[9] University of California,undefined

[10] The Mitochondrial and Metabolic Disease Center,undefined

[11] Departments of Medicine,undefined

[12] Pediatrics,undefined

[13] and Pathology,undefined

[14] University of North Carolina,undefined

[15] Gillings School of Global Public Health,undefined

[16] Department of Epidemiology,undefined

[17] Virginia Commonwealth University,undefined

[18] Department of Psychiatry,undefined

[19] Duke University Medical Center,undefined

[20] Veterans Affairs San Diego Healthcare System,undefined

[21] Veterans Affairs Center of Excellence for Stress and Mental Health,undefined

[22] VA Mid-Atlantic,undefined

[23] Mental Illness Research,undefined

[24] Education,undefined

[25] and Clinical Center,undefined

[26] Veterans Affairs Durham Healthcare System,undefined

[27] Duke University Medical Center,undefined

[28] Department of Psychiatry and Behavioral Sciences,undefined

[29] University Medical Center Utrecht,undefined

[30] Brain Center Rudolf Magnus,undefined

[31] State University of New York at Stony Brook,undefined

[32] Epidemiology Research Group,undefined

[33] Boston University,undefined

[34] School of Public Health,undefined

[35] Netherlands Ministry of Defence,undefined

[36] Brain Research and Innovation Centre,undefined

[37] McLean Hospital,undefined

[38] Division of Depression and Anxiety,undefined

[39] Harvard Medical School,undefined

[40] Duke University,undefined

[41] Department of Medicine,undefined

[42] Harvard T.H. Chan School of Public Health,undefined

[43] Department of Epidemiology,undefined

[44] Massachusetts General Hospital,undefined

[45] Psychiatric and Neurodevelopmental Genetics Unit,undefined

[46] Center for Human Genetic Research,undefined

[47] and Department of Psychiatry,undefined

[48] Broad Institute of MIT and Harvard,undefined

[49] Stanley Center for Psychiatric Research,undefined

[50] State University of New York at Stony Brook,undefined

来源：

Nature Communications | / 11卷

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摘要：

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.

引用

共 50 条

[1] Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR
Smith, Alicia K.
Ratanatharathorn, Andrew
Maihofer, Adam X.
Naviaux, Robert K.
Aiello, Allison E.
Amstadter, Ananda B.
Ashley-Koch, Allison E.
Baker, Dewleen G.
Beckham, Jean C.
Boks, Marco P.
Bromet, Evelyn
Dennis, Michelle
Galea, Sandro
Garrett, Melanie E.
Geuze, Elbert
Guffanti, Guia
Hauser, Michael A.
Katrinli, Seyma
Kilaru, Varun
Kessler, Ronald C.
Kimbrel, Nathan A.
Koenen, Karestan C.
Kuan, Pei-Fen
Li, Kefeng
Logue, Mark W.
Lori, Adriana
Luft, Benjamin J.
Miller, Mark W.
Naviaux, Jane C.
Nugent, Nicole R.
Qin, Xuejun
Ressler, Kerry J.
Risbrough, Victoria B.
Rutten, Bart P. F.
Stein, Murray B.
Ursano, Robert J.
Vermetten, Eric
Vinkers, Christiaan H.
Wang, Lin
Youssef, Nagy A.
Uddin, Monica
Nievergelt, Caroline M.
NATURE COMMUNICATIONS, 2020, 11 (01)
[2] Epigenome-wide association studies identify novel DNA methylation sites associated with PTSD: a meta-analysis of 23 military and civilian cohorts
Katrinli, Seyma
Wani, Agaz H.
Maihofer, Adam X.
Ratanatharathorn, Andrew
Daskalakis, Nikolaos P.
Montalvo-Ortiz, Janitza
Nunez-Rios, Diana L.
Zannas, Anthony S.
Zhao, Xiang
Aiello, Allison E.
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Avetyan, Diana
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Brick, Leslie A.
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Champagne, Frances A.
Chen, Chia-Yen
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Fatumo, Segun
Fortier, Catherine
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GENOME MEDICINE, 2024, 16 (01):
[3] LEVERAGING MULTI-OMIC DATA TO INTERPRET AN EPIGENOME-WIDE META-ANALYSIS OF PTSD IN 23 MILITARY AND CIVILIAN COHORTS
Smith, Alicia
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Zannas, Anthony S.
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Uddin, Monica
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EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2023, 75 : S40 - S41
[4] Epigenome-Wide Meta-Analysis of 13 Military and Civilian Cohorts Reveals Common and Cell-Type Specific DNA Methylation Patterns Associated With PTSD
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[5] Epigenome-Wide Meta-Analysis of 11 Military and Civilian Cohorts Reveals Cell-Type Specific and Inflammatory DNA Methylation Patterns Associated With PTSD
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[6] EPIGENOME-WIDE META-ANALYSIS OF > 3200 MILITARY AND CIVILIAN PARTICIPANTS IDENTIFIES CELL-TYPE SPECIFIC DNA METHYLATION SIGNALS ASSOCIATED WITH PTSD
Katrinli, Seyma
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Maihofer, Adam X.
Zhao, Ying
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EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2023, 75 : S70 - S71
[7] Epigenome-Wide Meta-Analysis of >2100 Military and Civilian Participants Reveals New DNA Methylation Patterns Associated With PTSD
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BIOLOGICAL PSYCHIATRY, 2022, 91 (09) : S342 - S343
[8] Epigenome-wide meta-analysis of PTSD symptom severity in three military cohorts implicates DNA methylation changes in genes involved in immune system and oxidative stress
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Monica Uddin
Molecular Psychiatry, 2022, 27 : 1720 - 1728
[9] Epigenome-wide meta-analysis of PTSD symptom severity in three military cohorts implicates DNA methylation changes in genes involved in immune system and oxidative stress
Katrinli, Seyma
Maihofer, Adam X.
Wani, Agaz H.
Pfeiffer, John R.
Ketema, Elizabeth
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MOLECULAR PSYCHIATRY, 2022, 27 (03) : 1720 - 1728
[10] Epigenome-Wide Meta-Analysis of BMI in Nine Cohorts: Examining Methylation as a Biomarker of BMI
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