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Home Health Mental Health

DNA methylation in Syrian refugees

May 29, 2025
in Mental Health
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Over the past few decades, we have become more aware of the profound and lasting impact of trauma on human health. Traumatic experiences can have rippling effects across communities and families, even affecting those that did not originally experience them.

But can the effects of trauma be passed down through generations and, if so, how? Research focusing on people exposed to extreme events, such as Holocaust survivors, support this idea, finding that survivors as well as their children are at greater risk of a number of mental health problems (Dashorst et al., 2019). There are many explanations for this “intergenerational inheritance of trauma” including social behaviours and parenting styles, but some scientists hypothesise that trauma alters our biology in a way that can be passed directly on to our children through DNA methylation.

DNA methylation is the addition of small molecules to sites throughout the genome. These molecules are added and removed throughout development and adulthood, in response to both internal signals from our body and external cues from environment around us. Methylation acts like dimmer switches for nearby genes, turning them up or down depending on these signals.

However, the inheritance of trauma via DNA methylation is a controversial topic, with limited evidence from human studies. A new paper published in Scientific Reports examines whether experiences of violence during war are biologically “written” into the DNA of Syrian refugee families through methylation and if so, whether these changes appear to be passed through multiple generations (Mulligan et al., 2025).

Our life experiences can alter the patterns of DNA methylation across our genome.

Our life experiences can alter the patterns of DNA methylation across our genome.

Methods

This study collected data from 48 Syrian families living in Jordan, totalling 131 grandmothers, mothers and children. The families had lived through war in either the 1980s or 2010s, or had moved to Jordan prior to 1980. This meant the researchers could assign everyone to a group according to their war exposure:

  • Direct exposure: grandmothers, mothers or children who had experienced war themselves.
  • Prenatal exposure: mothers or children whose mother had experienced war while pregnant with them.
  • Germline exposure: children whose grandmother had experienced war while pregnant with their mother (the egg that became the child will have already developed in their mother).
  • Control group: grandmothers, mothers or children who had not experienced war in any form.

Participants were also interviewed about their life events to count the number of different war-related or violent acts they had experienced.

DNA methylation was measured at over 850,000 sites across the genome from buccal (inner cheek) swabs and underwent standard quality control. DNA methylation from people in each war exposure group (direct, prenatal or germline) was compared to that of the control group using two different methods:

  1. Epigenome-wide association studies (EWAS): identifies single sites of the genome with differing DNA methylation levels. Nearby genes can tell us what biological consequences these differences likely have (Campagna et al., 2021).
  2. Epigenetic age acceleration: Epigenetic age is calculated from DNA methylation levels at specific sites across the genome. Acceleration (epigenetic age higher than chronological age) is often seen in people who have endured significant hardships or are suffering from chronic illnesses (Wang et al., 2022).

These analyses were adjusted for a small number of factors that may influence DNA methylation, including sex, age, the estimated proportion of skin cells in the buccal swabs, and genetic relatedness within families.

Results

Of the 131 study participants, 43 experienced war directly, 28 experienced war prenatally, 18 experienced war through the germline and 42 did not experience any war.

Out of the 768,625 sites that passed quality control, EWAS analyses found a small number of statistically significant differences in DNA methylation:

  • Syrian refugees who experienced war directly had different DNA methylation levels at 21 sites.
  • Syrian refugees who experienced war through the germline had different DNA methylation levels at 14 sites.
  • They found no DNA methylation differences in those that were exposed to war prenatally.

The researchers found that 32 of these 35 sites had DNA methylation differences in the same direction (higher or lower) across the different types of war exposure (although these were not statistically significant findings). This means that experiencing war at different developmental stages may have similar consequences, regardless of whether it is experienced directly or by an earlier generation.

Th researchers then looked at how DNA methylation at these 35 sites was related to the number of war-related events the individuals had experienced in their lives. They found that in many cases, the number of war-related events was correlated with DNA methylation. This means that not only is DNA methylation associated with any war exposure, but this relationship is also proportional with a greater burden of events having a larger impact on their DNA.

But what do these DNA methylation differences do? To attempt to answer this question the research team looked at the genes closest to these DNA methylation sites. Unfortunately, these genes didn’t have any functions or outcomes in common, preventing researchers from predicting their biological consequences. This means that while the researchers detected DNA methylation differences, we don’t know what they do or if they do anything at all.

Interestingly, they found limited convincing relationships between war exposure and epigenetic age. Only children exposed prenatally to war had some evidence of accelerated epigenetic ageing, meaning their epigenetic age appeared older than their chronological age. If the authors had controlled for the number of statistical tests they had performed, this would have likely only appeared due to chance. This suggests that war exposure in these groups has a minimal “ageing” effect compared to other types of traumatic experiences (Bourassa & Sbarra, 2024) and doesn’t appear to be passed on through generations.

War exposure experienced either directly or by a person’s pregnant grandparent was associated with different DNA methylation levels at 35 different sites across the genome. But it is unclear what effect these differences actually have on the individual’s health.

War exposure experienced either directly or by a person’s pregnant grandparent was associated with different DNA methylation levels at 35 different sites across the genome. But it is unclear what effect these differences actually have on the individual’s health.

Conclusions

The authors state:

this is the first report of an intergenerational epigenetic signature of violence.

This work provides further evidence that traumatic experiences like war and violence may lead to lasting biological differences, although these have yet to be linked to any differences in function or health. This work also suggests that these biological differences could be found in multiple generations, regardless of when they were exposed to war, hinting at intergenerational inheritance. However further research is needed to understand whether this truly represents “the inheritance of trauma”.

War exposure has similar modest associations with DNA methylation across three different generations, but does this mean that it can be passed down from grandmother to grandchild?

War exposure has similar modest associations with DNA methylation across three different generations, but does this mean that it can be passed down from grandmother to grandchild?

Strengths and limitations

The main strengths of this study lie in its unique population and study design. Studying these families of Syrian refugees allowed the research team to capture real-world exposure to extreme adversity which occurred in defined periods of time. This would be impossible for researchers to mimic artificially and provides much needed information about the potential consequences of war, an unfortunately common experience worldwide (ACLED, 2024). The multigenerational design allowed the researchers to compare groups who experienced the same wars either directly, prenatally or via the germline. Most epigenetic studies only look at one or two generations which prevents this comparison. Finally, the researchers used well established DNA methylation measurement techniques with appropriate statistical controls for multiple testing and family structure in their EWAS analyses.

However, there are several limitations which prevent this study from contributing more to our understanding of intergenerational inheritance of trauma.

Small sample size: Although a valuable study, 60-85 people are modest samples for an EWAS, which commonly include hundreds if not thousands of people. Small samples are prone to both false positives and false negatives when comparing hundreds of thousands of data points and findings may not replicate in larger populations.

Correlation, not causation: A wide-spread problem with observational studies like these is that we cannot say for certain that war exposure caused the DNA methylation differences seen here. There may be many other unmeasured factors which differ between the groups, particularly as the control group has lived in Jordan for significantly longer. This could include several things such as nutrition, physical health, or socio-economic differences between exposed and control groups.

A snapshot in time: This study could only measure DNA methylation at a single point in time, which prevents us from knowing exactly when these methylation differences occurred and if any others have been lost over time. This information is necessary to confirm if patterns are truly inherited directly through the germline or whether they appeared at another point in time before testing.

The study found DNA methylation differences in groups that experienced war at one specific point in time, but when did these changes actually happen and what caused them?

The study found DNA methylation differences in groups that experienced war at one specific point in time, but when did these changes actually happen and what caused them?

Implications for practice

This important study adds to a growing but controversial research area suggesting that trauma can leave marks on the genome that persist across generations. Previous studies of genocide survivors (Rivera et al., 2024), Holocaust survivors (Yehuda et al., 2016) and famine survivors (Heijmans et al., 2008) have reported similar methylation changes in offspring, but this study by Mulligan and colleagues adds evidence that similar methylation patterns are found in a third generation. Despite the interesting findings, a number of questions will need to be answered before this research can be applied.

Do methylation differences matter? An increasing number of studies have found DNA methylation differences associated with traumatic experiences like war (including my own – full disclosure; Smeeth et al., 2023), but in most cases, we don’t know what these do. The control of the genome is incredibly complex, and different patterns of methylation don’t automatically translate into noticeable health outcomes. Compounding this problem is the fact that many of the methylation differences are incredibly small, despite being “statistically significant”.

Are these biological representations of trauma? Labelling these methylation changes as signatures of “trauma” are potentially simplistic and may overemphasise the threat to future generations. While the experiences of the study participants are undoubtedly traumatic, the biology they measured doesn’t directly capture psychological trauma. It captures differences in methylation between groups that had vastly different experiences which could include displacement, poverty, or illness in addition to war. DNA methylation differences could arise from any of these factors and may even represent adaptive changes meant to protect the individual from further harm rather than representing a molecular “wound” (Liu, 2015).

Can methylation patterns be inherited? While similar DNA methylation patterns were seen across different generations, whether these patterns can be transmitted from the germline to later life is highly contested (Horsthemke, 2018). Methylation patterns are generally wiped clean during fertilisation of the egg. Some areas are spared, but it has yet to be shown whether these overlap with those impacted by traumatic experiences.

Despite these remaining questions, this study is an important piece in a complicated and ongoing investigation into how life experiences shape our biology and future generations. While we can’t say for certain that DNA passes on trauma to further generations, it provides a starting point for more informed and targeted research into this phenomenon. Critically, the lack of concrete evidence for direct biological inheritance of trauma does not take away from the real and lasting impacts that traumatic experiences like war have on communities and families.

More research is needed to uncover what molecular mechanisms are impacted by war and trauma.

Statement of interests

Demelza has previously worked on similar research examining DNA methylation and war exposure in Syrian refugee children, but she did not have any personal involvement in this study.

Acknowledgments

Thanks to Professor Michael Pluess for reviewing this blog and providing constructive feedback.

Links

Primary paper

Mulligan, C. J., Quinn, E. B., Hamadmad, D., Dutton, C. L., Nevell, L., Binder, A. M., Panter-Brick, C., & Dajani, R. (2025). Epigenetic signatures of intergenerational exposure to violence in three generations of Syrian refugees. Scientific Reports, 15(1), 5945. https://doi.org/10.1038/s41598-025-89818-z

Other references

ACLED. (2024). Conflict Index: December 2024. Global conflicts double over the past five years. https://acleddata.com/conflict-index/index-december-2024/

Bourassa, K. J., & Sbarra, D. A. (2024). Trauma, adversity, and biological aging: Behavioral mechanisms relevant to treatment and theory. Translational Psychiatry, 14(1), 1–13. https://doi.org/10.1038/s41398-024-03004-9

Campagna, M. P., Xavier, A., Lechner-Scott, J., Maltby, V., Scott, R. J., Butzkueven, H., Jokubaitis, V. G., & Lea, R. A. (2021). Epigenome-wide association studies: Current knowledge, strategies and recommendations. Clinical Epigenetics, 13(1), 214. https://doi.org/10.1186/s13148-021-01200-8

Dashorst, P., Mooren ,Trudy M., Kleber ,Rolf J., de Jong ,Peter J., & and Huntjens, R. J. C. (2019). Intergenerational consequences of the Holocaust on offspring mental health: A systematic review of associated factors and mechanisms. European Journal of Psychotraumatology, 10(1), 1654065. https://doi.org/10.1080/20008198.2019.1654065

Liu, R. T. (2015). A developmentally informed perspective on the relation between stress and psychopathology: When the problem with stress is that there is not enough. Journal of Abnormal Psychology, 124(1), 80–92. https://doi.org/10.1037/abn0000043

Smeeth, D., McEwen, F. S., Popham, C. M., Karam, E. G., Fayyad, J., Saab, D., Rieder, M. J., Elzagallaai, A. A., van Uum, S., & Pluess, M. (2023). War exposure, post-traumatic stress symptoms and hair cortisol concentrations in Syrian refugee children. Molecular Psychiatry, 28(2), 647–656. https://doi.org/10.1038/s41380-022-01859-2

Wang, K., Liu, H., Hu, Q., Wang, L., Liu, J., Zheng, Z., Zhang, W., Ren, J., Zhu, F., & Liu, G.-H. (2022). Epigenetic regulation of aging: Implications for interventions of aging and diseases. Signal Transduction and Targeted Therapy, 7(1), 1–22. https://doi.org/10.1038/s41392-022-01211-8

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