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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.
Afiliação
  • Smith AK; Emory University, Department of Gynecology and Obstetrics, Atlanta, GA, USA. alicia.smith@emory.edu.
  • Ratanatharathorn A; Emory University, Department of Psychiatry & Behavioral Sciences, Atlanta, GA, USA. alicia.smith@emory.edu.
  • Maihofer AX; Columbia University, Department of Epidemiology, New York, NY, USA.
  • Naviaux RK; University of California San Diego, Department of Psychiatry, La Jolla, CA, USA.
  • Aiello AE; University of California, The Mitochondrial and Metabolic Disease Center, Departments of Medicine, Pediatrics, and Pathology, San Diego, CA, USA.
  • Amstadter AB; University of North Carolina, Gillings School of Global Public Health, Department of Epidemiology, Chapel Hill, NC, USA.
  • Ashley-Koch AE; Virginia Commonwealth University, Department of Psychiatry, Richmond, VA, USA.
  • Baker DG; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
  • Beckham JC; University of California San Diego, Department of Psychiatry, La Jolla, CA, USA.
  • Boks MP; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
  • Bromet E; Veterans Affairs Center of Excellence for Stress and Mental Health, San Diego, CA, USA.
  • Dennis M; VA Mid-Atlantic, Mental Illness Research, Education, and Clinical Center, Durham, NC, USA.
  • Galea S; Veterans Affairs Durham Healthcare System, Durham, NC, USA.
  • Garrett ME; Duke University Medical Center, Department of Psychiatry and Behavioral Sciences, Durham, NC, USA.
  • Geuze E; University Medical Center Utrecht, Brain Center Rudolf Magnus, Utrecht, The Netherlands.
  • Guffanti G; State University of New York at Stony Brook, Epidemiology Research Group, Stony Brook, NY, USA.
  • Hauser MA; VA Mid-Atlantic, Mental Illness Research, Education, and Clinical Center, Durham, NC, USA.
  • Katrinli S; Duke University Medical Center, Department of Psychiatry and Behavioral Sciences, Durham, NC, USA.
  • Kilaru V; Boston University, School of Public Health, Boston, MA, USA.
  • Kessler RC; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
  • Kimbrel NA; University Medical Center Utrecht, Brain Center Rudolf Magnus, Utrecht, The Netherlands.
  • Koenen KC; Netherlands Ministry of Defence, Brain Research and Innovation Centre, Utrecht, The Netherlands.
  • Kuan PF; McLean Hospital, Division of Depression and Anxiety, Belmont, MA, USA.
  • Li K; Harvard Medical School, Boston, MA, USA.
  • Logue MW; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
  • Lori A; Duke University, Department of Medicine, Durham, NC, USA.
  • Luft BJ; Emory University, Department of Gynecology and Obstetrics, Atlanta, GA, USA.
  • Miller MW; Emory University, Department of Gynecology and Obstetrics, Atlanta, GA, USA.
  • Naviaux JC; Harvard Medical School, Boston, MA, USA.
  • Nugent NR; VA Mid-Atlantic, Mental Illness Research, Education, and Clinical Center, Durham, NC, USA.
  • Qin X; Veterans Affairs Durham Healthcare System, Durham, NC, USA.
  • Ressler KJ; Duke University Medical Center, Department of Psychiatry and Behavioral Sciences, Durham, NC, USA.
  • Risbrough VB; Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, MA, USA.
  • Rutten BPF; Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, and Department of Psychiatry, Boston, MA, USA.
  • Stein MB; Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA.
  • Ursano RJ; State University of New York at Stony Brook, Department of Applied Mathematics and Statistics, Stony Brook, NY, USA.
  • Vermetten E; University of California, The Mitochondrial and Metabolic Disease Center, Department of Medicine, San Diego, CA, USA.
  • Vinkers CH; National Center for PTSD, Behavioral Science Division at VA Boston Healthcare System, Boston, MA, USA.
  • Wang L; Boston University School of Medicine, Department of Psychiatry, Boston, MA, USA.
  • Youssef NA; Boston University School of Medicine, Department of Medicine (Biomedical Genetics), Boston, MA, USA.
  • Uddin M; National Center for PTSD, Behavioral Science Division at VA Boston Healthcare System, Boston, MA, USA.
  • Nievergelt CM; Boston University School of Medicine, Department of Psychiatry, Boston, MA, USA.
Nat Commun ; 11(1): 5965, 2020 11 24.
Article em En | MEDLINE | ID: mdl-33235198
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Transtornos de Estresse Pós-Traumáticos / Metilação de DNA / Fatores de Transcrição Hélice-Alça-Hélice Básicos Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Female / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Transtornos de Estresse Pós-Traumáticos / Metilação de DNA / Fatores de Transcrição Hélice-Alça-Hélice Básicos Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Female / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article