PTSD is Associated with Advanced Epigenetic Age in 45,091 US Military Veterans
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Background
Posttraumatic stress disorder (PTSD) has been associated with advanced biological age in DNA methylation data, but results have been inconsistent. This study evaluated PTSD in association with epigenetic age in the largest cohort to date (by ∼20 fold).
Methods
Participants were 45,091 US Veterans (92.76% male) enrolled in the VA’s Million Veteran Program, with VA electronic health record (EHR), self-report PTSD severity ( n = 22,835), and DNA methylation and genotype data. PTSD diagnoses predated the blood draw for obtaining DNA by ≥ one year.
Results
PTSD diagnosis, severity, and duration were associated with age-adjusted metrics of epigenetic age (“age residuals”) per the Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE epigenetic age algorithms after multiple testing adjustment. The strongest and most robust effect (to additional covariates) was evident for PTSD severity in association with GrimAge residuals (B = .029, adjusted- p = 2.48e-53, up to ∼ 2 years advanced age). The relationships between PTSD severity and GrimAge and PhenoAge residuals were stronger among younger vs. older Veterans. In stratified analyses, all PTSD variables were associated with all epigenetic age residuals in the European ancestry subgroup ( n = 27,578), but significant associations only emerged for GrimAge and DunedinPACE in the African ancestry participants ( n = 11,690).
Conclusions
PTSD was associated with advanced epigenetic aging in the largest study to date to evaluate this question. Effects were generally small in magnitude, though meaningful when considering the personal and healthcare system impact of advanced aging in the large population of VA users with PTSD.
