# Identifying DNA Methylation Alterations of Chronic Effects Of Blast and Disturbed Sleep

> **NIH VA I01** · JAMES J PETERS VA  MEDICAL CENTER · 2024 · —

## Abstract

SUMMARY
Traumatic brain injury (TBI) is a significant cause of death and disease in the armed forces, and it has been estimated
that 10-20% of returning Operation Iraqi Freedom/Operation Enduring Freedom (Afghanistan) Veterans have
suffered a TBI, with many having symptoms suggestive of the residual effects of mild TBIs (mTBIs) not recognized
prior to discharge. In recognition of the latent residual effects of repeated exposures to blast, one of which may be
mTBI, The 2020 National Defense Authorization Act includes a provision mandating documentation of blast exposure
during both training and combat to inform future risk mitigation. The focus of the proposed study is to investigate the
effects of exposures to blast and related symptomology incurred during operational training. In collaboration with DoD
Walter Reed Army Institute of Research (WRAIR) investigators, we have obtained a critical mass of anonymized
blood samples from military and law enforcement personnel from operational blast training courses, which will allow
us to perform systematic DNA methylation and transcriptional studies. We have 2387 biological sample specimens
along with demographic, symptom, and blast sensor data from both breaching and large caliber rifle protocols
reflecting the exposures incurred by Veterans who because of their specific military occupational specialty (MOS)
have repeated occupational overpressure exposure (ROPE), resulting in increased susceptibility to mTBI and
associated symptoms. The overarching goal of this study is to link transcriptional regulatory perturbations associated
with cumulative exposure to blast to chronic co-occurring physiological and psychological symptoms. Converging
evidence in the field and from our own research has revealed molecular perturbations associated with ROPE.
Specifically, we have shown blast associated alterations in DNA methylation (a highly stable epigenetic mark) in
genes involved in sleep and circadian functioning, motivating our in-depth phenotyping of sleep disturbance in
Veterans with ROPE in the proposed study. Here we will pursue the following aims: 1) Identify DNA methylation
perturbations associated with cumulative occupational exposure to blast in ongoing cohorts; 2) Identify DNA
methylation patterns that track with ROPE and associated physiological and psychological symptoms in ongoing
cohorts; and 3) Identify altered DNA methylation patterns associated with cumulative blast in Veterans with MOS
exposed to occupational blast newly recruited for this study. DNA methylation and transcriptional patterns in loci
identified in the first 2 aims will be investigated in Veterans recruited with MOS involving varying durations and
spectrum of exposures to occupational blast to determine whether these loci are also associated with cumulative
blast and related clinical symptoms including sleep disturbance, with comorbid mTBI, PTSD and/or Major
Depressive Disorder in these Veterans This will allow us to causally link ...

## Key facts

- **NIH application ID:** 10834945
- **Project number:** 5I01RX003818-03
- **Recipient organization:** JAMES J PETERS VA  MEDICAL CENTER
- **Principal Investigator:** FATEMEH G HAGHIGHI
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834945

## Citation

> US National Institutes of Health, RePORTER application 10834945, Identifying DNA Methylation Alterations of Chronic Effects Of Blast and Disturbed Sleep (5I01RX003818-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10834945. Licensed CC0.

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