Abstract
Importance: Exposure to war is associated with poor mental health outcomes. Adverse and traumatic experiences can lead to long-lasting DNA methylation (DNAm) changes, potentially mediating the link between adversity and mental health. To date, limited studies have investigated the impact of war on DNAm in children or adolescents, hampering our understanding of the biological impact of war exposure.
Objective: To identify salivary DNAm differences associated with war exposure in refugee children and adolescents.
Design, Setting, and Participants: 1507 Syrian refugee children and adolescent and their primary caregiver were recruited from tented settlements in Lebanon. Data collection was carried out in two waves, one year apart from October 2017 to January 2018 and October 2018 to January 2019. Children and their caregiver were interviewed and children provided saliva samples for DNA extraction (Y1: 1449, Y2:872). Data analysis was conducted in 2022 and 2023.
Main Outcomes and Measures: Salivary DNAm levels were assayed with Illumina-Infinium Human Methylation EPIC BeadChip and war exposure was assessed by child and caregiver questionnaires. Epigenetic ageing acceleration was estimated using a set of preexisting epigenetic ageing clocks. A literature search was conducted to identify previously reported DNAm correlates of childhood trauma.
Results: The study population included 1507 children and adolescents (Mage=11.3, 6-19 years old, 47.4% male). Children who reported war events had a number of differentially methylated sites and regions. Enrichment analyses indicated an enrichment of gene sets related to transmembrane transport, neurotransmission, and intracellular movement in genes that exhibited differential methylation. Sex-stratified analyses found a number of sex-specific DNAm differences associated with war exposure. Only two (out of 258) previously reported trauma- associated DNAm sites were associated with war exposure [B=-.004, 95% CI -.005 to -.003, pBonf= .037; B=-.005, 95% CI -.006 to -.004, pBonf= .026]. Any war exposure or bombardment was nominally associated with decreased epigenetic age using Horvath’s multi-tissue clock [B=-.39, 95% CI -.63 to -.14; p = .007; B=-.42, 95% CI -.73 to -.11; p = .002].
Conclusions and Relevance: In this cohort of Syrian refugee children and adolescents, war exposure is associated with a small number of distinct differences in salivary DNAm.