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War Exposure Linked to Epigenetic Changes in Syrian Refugee Children

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NEW YORK – Being exposed to war during childhood can alter epigenetic regulation of genes involved in neurotransmission, intracellular transport, transmembrane transport, and other processes, according to new research led by a team at the University of Surrey.

Together, the findings suggested that "traumatic experiences can change our biology and may therefore have long-lasting effects that impact on the development of children," senior and corresponding author Michael Pluess, a researcher at the University of Surrey, said in an email.

For a paper appearing in JAMA Psychiatry on Wednesday, Pluess and colleagues in the UK and Lebanon used array-based DNA methylation profiling to evaluate saliva samples from more than 1,500 Syrian refugee children between the ages of 6 and 19 years with different war experiences. The children were living in informal, tented settlements in Lebanon and enrolled through a cohort study called BIOPATH that kicked off in 2017.

The team also used data from questionnaires completed by the children and their caregivers to get a sense of the children's exposure to war conditions.

Based on DNA methylation data for 1,449 children who shared samples in the first year of the study and 872 children sampled in the second year, the investigators saw a handful of sites or regions with DNA methylation differences that were associated with total war exposure, any war exposure, war-related violence in the home, or other experiences linked to war.

While methylation dipped at the cg08095654 locus in children with any exposure to war, for example, war-related violence at home coincided with an uptick in methylation at the cg18691565 locus. A differentially methylated region on chromosome 19, meanwhile, turned up in children reporting any war exposure.

The methylation shifts were particularly prominent in genes related to stress response and brain development in girls, who appeared to have enhanced biological changes in response to war exposure.

While their subsequent enrichment analyses highlighted genes involved in neurotransmission and cell transport, Pluess noted that additional research will be needed to narrow in on the mechanisms behind the epigenetic effects of war exposure and to track their biological and psychological consequences and stability over time.

More broadly, the investigators' epigenetic clock analyses hinted that war exposure tended to coincide with dialed-down epigenetic aging. The results went against the accelerated epigenetic aging effects originally hypothesized, prompting them to speculate that war-related adversity may impair childhood development.

The team saw only limited overlap with methylation changes previously implicated in studies of epigenetic responses to bullying, poverty, or other types of trauma, consistent with some degree of trauma-related specificity to the epigenetic shifts.

"[O]ur results seem to be unique to our sample population of Syrian refugee children, and different kinds of trauma are associated with different methylation changes," Pluess said, adding that it is also possible that the results "may simply be difficult to replicate for methodological reasons."

He noted that the researchers now plan to explore relationships between DNA methylation and individual genetic differences. In addition, they want to study the effects of nurturing circumstances such as supportive parenting or communities on DNA methylation profiles over time in the children from the Syrian refugee population.