Epigenetic signatures of intergenerational exposure to violence in three generations of Syrian refugees
Open accessAbstract
Maternal trauma influences infant and adult health outcomes and may impact future generations through epigenetic modifications such as DNA methylation (DNAm). Research in humans on the intergenerational epigenetic transmission of trauma effects is limited. In this study, we assessed DNAm signatures of war-related violence by comparing germline, prenatal, and direct exposures to violence across three generations of Syrian refugees. We compared families in which a pregnant grandmother versus a pregnant mother was exposed to violence and included a control group with no exposure to war. We collected buccal swab samples and survey data from mothers and 1-2 children in each of 48 families (n = 131 participants). Based on an epigenome-wide association study (EWAS), we identified differentially methylated regions (DMPs): 14 were associated with germline and 21 with direct exposure to violence. Most DMPs showed the same directionality in DNAm change across germline, prenatal, and direct exposures, suggesting a common epigenetic response to violence. Additionally, we identified epigenetic age acceleration in association with prenatal exposure to violence in children, highlighting the critical period of in utero development. This is the first report of an intergenerational epigenetic signature of violence, which has important implications for understanding the inheritance of trauma.
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Consistent directional methylation changes across direct, prenatal, and germline exposure, together with dose-response relationships between trauma burden and molecular changes, support cumulative biological adaptation to prolonged adversity.
“Consistent directional methylation changes across direct, prenatal, and germline exposure, together with dose-response relationships between trauma burden and molecular changes, support cumulative biological adaptation to prolonged adversity (59).”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [59]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredAcross war-exposed populations, chronic trauma has been associated with epigenetic modulation of pathways governing cellular metabolism, neural development, and adaptive stress responses.
“Across war-exposed populations, chronic trauma has been associated with epigenetic modulation of pathways governing cellular metabolism, neural development, and adaptive stress responses.”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [59]
The Results (Epigenome wide association study; page not provided) associate violence exposure in Syrian refugees with DNA-methylation differences and report that additional trauma was linked to further shifts at most identified sites. But the same section reports no enrichment for biological processes, so it does not establish modulation of the specified cellular-metabolism, neural-development, and adaptive-stress pathways. The Discussion describes enhanced responses to future stress as a possibility, not a demonstrated pathway effect. (LLM, conf=0.87)
Experimental — accuracy not yet measuredDifferential DNA methylation in genes involved in mitochondrial energy regulation, intracellular transport, and neurodevelopment suggests integration of metabolic and neuroregulatory systems under prolonged adversity.
“Differential DNA methylation in genes involved in mitochondrial energy regulation, intracellular transport, and neurodevelopment suggests integration of metabolic and neuroregulatory systems under prolonged adversity (58, 59).”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [59]
The Results (Epigenome wide association study; page unavailable) report differential DNA methylation associated with violence exposure and identify a site annotated to RAB43, a gene involved in membrane trafficking. Our copy does not link the identified sites to mitochondrial energy regulation or neurodevelopment, and the Results report no enrichment for biological processes. The proposed integration of metabolic and neuroregulatory systems is therefore not supported by this paper. (LLM, conf=0.85)
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- Authors
- Mulligan, C. J., Quinn, E. B., Hamadmad, D., Dutton, C. L., Nevell, L., Binder, A. M., Panter-Brick, C., & Dajani, R.
- Affiliations
- University of Florida (US)
- University of Hawaii System (US)
- Hashemite University (JO)
- Corresponding author
- Mulligan, Connie J.
- ORCID
- Venue
- Scientific Reports
- Published
- 2025-02-27
- Volume
- 15
- Issue
- 1
- Pages
- 5945-5945
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC11868390
- OpenAlex
- W4408062891
- Cited by
- 36
- References
- 76
- Citations by year
- 2026: 17 · 2025: 19
- FWCI
- 10.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- war-related violence, Syrian refugees, DNA methylation, maternal trauma, differentially methylated regions, epigenetic age acceleration, buccal swab DNA
- MeSH terms
- Grandparents, Exposure to Violence, Adult, Child, Child, Preschool, Female, Humans, Infant, Male, Mothers, Pregnancy, Prenatal Exposure Delayed Effects, Refugees, Syria, DNA Methylation, Epigenesis, Genetic, Genome-Wide Association Study
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