Zeyuan Wang1, Qin Hui, Jack Goldberg, Nicholas Smith, Belal Kaseer, Nancy Murrah, Oleksiy M Levantsevych, Lucy Shallenberger, Emily Diggers, J Douglas Bremner, Viola Vaccarino, Yan V Sun. 1. From the Department of Epidemiology (Wang, Hui, Kaseer, Murrah, Levantsevych, Shallenberger, Diggers, Vaccarino, Sun), Emory University Rollins School of Public Health, Atlanta, Georgia; Vietnam Era Twin Registry, Seattle Epidemiologic Research and Information Center, US Department of Veterans Affairs (Goldberg, Smith), Seattle, Washington; Departments of Psychiatry and Behavioral Sciences and Radiology and Imaging Sciences (Bremner), Emory University School of Medicine, Atlanta, Georgia; and Atlanta VA Health Care System (Bremner, Sun), Decatur, Georgia.
Abstract
OBJECTIVE: Posttraumatic stress disorder (PTSD) has been related to accelerated biological aging processes, but objective evidence for this association is limited. DNA methylation (DNAm) age acceleration is a novel measure of biological aging that may help clarify if PTSD is related to biological aging processes. We aim to examine whether PTSD is associated with biological aging using a comprehensive set of DNAm age acceleration markers and to what extent the unshared environment contributes to the association. METHODS: Using a cross-sectional co-twin control study design, we investigated the association of the clinical diagnosis and symptom severity of PTSD with six measurements of DNAm age acceleration based on epigenome-wide data derived from peripheral blood lymphocytes of 296 male twins from the Vietnam Era Twin Registry. RESULTS: Twins with current PTSD had significantly advanced DNAm age acceleration compared with twins without PTSD for five of six measures of DNAm age acceleration. Across almost all measures of DNAm age acceleration, twins with current PTSD were "epigenetically older" than their twin brothers without PTSD: estimated differences ranged between 1.6 (95% confidence interval = 0.0-3.1) and 2.7 (95% confidence interval = 0.5-4.8) biological age year-equivalents. A higher Clinician-Administered PTSD Scale score was also associated with a higher within-pair DNAm age acceleration. Results remained consistent after adjustment for behavioral and cardiovascular risk factors. CONCLUSIONS: PTSD is associated with epigenetic age acceleration, primarily through unshared environmental mechanisms as opposed to genetic or familial factors. These results suggest that PTSD is related to systemic processes relevant to biological aging.
OBJECTIVE: Posttraumatic stress disorder (PTSD) has been related to accelerated biological aging processes, but objective evidence for this association is limited. DNA methylation (DNAm) age acceleration is a novel measure of biological aging that may help clarify if PTSD is related to biological aging processes. We aim to examine whether PTSD is associated with biological aging using a comprehensive set of DNAm age acceleration markers and to what extent the unshared environment contributes to the association. METHODS: Using a cross-sectional co-twin control study design, we investigated the association of the clinical diagnosis and symptom severity of PTSD with six measurements of DNAm age acceleration based on epigenome-wide data derived from peripheral blood lymphocytes of 296 male twins from the Vietnam Era Twin Registry. RESULTS: Twins with current PTSD had significantly advanced DNAm age acceleration compared with twins without PTSD for five of six measures of DNAm age acceleration. Across almost all measures of DNAm age acceleration, twins with current PTSD were "epigenetically older" than their twin brothers without PTSD: estimated differences ranged between 1.6 (95% confidence interval = 0.0-3.1) and 2.7 (95% confidence interval = 0.5-4.8) biological age year-equivalents. A higher Clinician-Administered PTSD Scale score was also associated with a higher within-pair DNAm age acceleration. Results remained consistent after adjustment for behavioral and cardiovascular risk factors. CONCLUSIONS: PTSD is associated with epigenetic age acceleration, primarily through unshared environmental mechanisms as opposed to genetic or familial factors. These results suggest that PTSD is related to systemic processes relevant to biological aging.
Authors: Andrew E Teschendorff; Usha Menon; Aleksandra Gentry-Maharaj; Susan J Ramus; Daniel J Weisenberger; Hui Shen; Mihaela Campan; Houtan Noushmehr; Christopher G Bell; A Peter Maxwell; David A Savage; Elisabeth Mueller-Holzner; Christian Marth; Gabrijela Kocjan; Simon A Gayther; Allison Jones; Stephan Beck; Wolfgang Wagner; Peter W Laird; Ian J Jacobs; Martin Widschwendter Journal: Genome Res Date: 2010-03-10 Impact factor: 9.043
Authors: J D Bremner; P Randall; T M Scott; R A Bronen; J P Seibyl; S M Southwick; R C Delaney; G McCarthy; D S Charney; R B Innis Journal: Am J Psychiatry Date: 1995-07 Impact factor: 18.112
Authors: Benjamin Lehne; Alexander W Drong; Marie Loh; Weihua Zhang; William R Scott; Sian-Tsung Tan; Uzma Afzal; James Scott; Marjo-Riitta Jarvelin; Paul Elliott; Mark I McCarthy; Jaspal S Kooner; John C Chambers Journal: Genome Biol Date: 2015-02-15 Impact factor: 13.583