# Methylome profile of World Trade Center related PTSD

> **NIH ALLCDC U01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $499,622

## Abstract

ABSTRACT
The 9/11 World Trade Center terrorist attack was a massive disaster, resulting in long-term psychological trauma
to the responders, with 17% of responders experiencing symptoms consistent with PTSD more than two decades
later. DNA methylation, the most widely studied epigenetic mark can illuminate gene-environment interaction
and provide biological insights into the etiology and maintenance of PTSD. Although a number of epigenome-
wide association studies (EWAS) have been conducted to identify CpGs associated with PTSD, many of these
studies are underpowered. Ongoing efforts to address small sample sizes of individual cohort include
establishing the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup, which is the largest
epigenetic consortium to date. Large sample EWAS in peripheral blood are feasible and have the potential to
identify accessible biomarker for PTSD, however these studies also highlight the need for more data and stronger
designs. Specifically, the limitations of PGC include large methodological heterogeneity of the participating study
cohorts. The proposed study builds on existing studies by using more powerful design that will produce novel
findings, and at the same time allow new data to be combined with PGC data to further increase power and
ensure generalizability of the results. To this end, genome-wide methylation profiling with the Illumina Infinium
MethylationEPIC BeadChip arrays will be generated using biobanked blood samples on a subset of n=1,850
responders who have been genotyped. In Aim 1, EWAS will be performed to identify CpGs associated with PTSD
and PTSD dimensions. In Aim 2, genetic variants associated with methylation will be derived via methylation
quantitative trait loci analysis and integrated with PTSD genetic risk variants to identify putatively causal CpGs
and variants for PTSD. In Aim 3, results from the proposed study will be combined with the PGC results to
maximize power to detect generalizable findings. To enhance the impact of this study, an exploratory aim is
included to identify methylation subclasses associated with PTSD and health outcomes. This will be the largest
single-cohort PTSD study and is powered to identify novel epigenetic mechanisms that maintain symptoms in
chronic PTSD. This research will help to explicate pathophysiology of this disorders on molecular level, which
may become targets for treatment development.

## Key facts

- **NIH application ID:** 10903703
- **Project number:** 5U01OH012466-02
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Pei-Fen Kuan
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2024
- **Award amount:** $499,622
- **Award type:** 5
- **Project period:** 2023-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903703

## Citation

> US National Institutes of Health, RePORTER application 10903703, Methylome profile of World Trade Center related PTSD (5U01OH012466-02). Retrieved via AI Analytics 2026-06-05 from https://api.ai-analytics.org/grant/nih/10903703. Licensed CC0.

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