No association between war-related trauma or PTSD symptom severity and epigenome-wide DNA methylation in Burundian refugees

ABSTRACT

Background: War-related trauma is associated with varying posttraumatic stress disorder (PTSD) prevalence rates in refugees. In PTSD development, differential DNA methylation (DNAm) levels associated with trauma exposure might be involved in risk versus resilience processes. Studies investigating DNAm profiles related to trauma exposure and PTSD among refugees remain sparse.

Objective: The present epigenome-wide association study investigated associations between war-related trauma, PTSD, and altered DNAm patterns in Burundian refugee families with 110 children and their 207 female and male caregivers.

Method: War-related trauma load and PTSD symptom severity were assessed in structured clinical interviews with standardised instruments. Epigenome-wide DNAm levels were quantified from buccal epithelia using the Illumina EPIC beadchip.

Results: Controlling for biological confounders, no significant epigenome-wide DNAm alterations associated with trauma exposure or PTSD were identified in children or caregivers (FDRs > .05). Co-methylated positions derived as modules from weighted gene correlation network analyses were not significantly associated with either war-related trauma experience in children or caregivers or with PTSD.

Conclusions: These results do not provide evidence for altered DNAm patterns associated with exposure to war-related trauma or PTSD.

HIGHLIGHTS

• The study examines an understudied population in epigenome-wide association studies.

• Burundian refugees’ war-trauma, PTSD, and DNA methylation were studied.

• Epigenome-wide DNA methylation was not significantly associated with war-trauma or PTSD in the conflict-affected sample.

Antecedentes: El trauma relacionado con la guerra se asocia con diferentes tasas de prevalencia de trastorno de Estrés postraumático (TEPT) en refugiados. En el desarrollo del TEPT, los niveles diferenciales de metilación del ADN (ADNm) con exposición al trauma podrían estar involucrados en los procesos de riesgo versus resiliencia. Los estudios que investigan los perfiles de ADNm relacionados con la exposición al trauma y TEPT entre refugiados siguen siendo escasos.

Objetivo: El presente estudio de asociación de todo el epigenoma investigó las asociaciones entre el trauma relacionado con la guerra, TEPT y patrones de ADNm alterados en familias de refugiados de Burundi con 110 niños y sus 207 cuidadores femeninos y masculinos.

Método: La carga traumática relacionada con la guerra y la gravedad de los síntomas del TEPT se evaluaron en entrevistas clínicas estructuradas con instrumentos estandarizados. Los niveles de ADNm de todo el epigenoma fueron cuantificados a partir del epitelio bucal utilizando el chip de cuentas Illlumina EPIC.

Resultados: Al controlar los factores de confusión biológicos, no se identificaron alteraciones significativas en el ADNm en todo el epigenoma asociadas con la exposición al trauma o TEPT en niños o cuidadores (FDRs > .05). Las posiciones co-metiladas derivadas como módulos de los análisis de redes de correlación de genes ponderados no se asociaron significativamente ni con experiencias traumáticas relacionadas con la guerra en niños o cuidadores ni con TEPT.

Conclusiones: Estos resultados no proporcionan evidencia de patrones de ADNm alterados asociados con la exposición a traumas relacionados con la guerra o TEPT.

背景：难民中战争相关创伤与不同的创伤后应激障碍 (PTSD) 流行率有关。 在 PTSD 发展中，与创伤暴露相关的不同 DNA 甲基化 (DNAm) 水平可能涉及风险或恢复过程。考查难民中创伤暴露和PTSD相关的 DNAm 剖面的研究仍然很少。

目的：本全表观基因组关联研究考查了布隆迪难民家庭（110 名儿童及其 207名女性和男性照顾者）中战争相关创伤、PTSD 和改变的 DNAm 模式之间的关联。

方法：在使用标准化工具的结构化临床访谈中对战争相关创伤负荷和 PTSD 症状严重程度进行评估。使用 Illumina EPIC 珠芯片从口腔上皮细胞中量化全表观基因组DNAm水平。

结果：控制生物混杂因素后，在儿童或看护者中未发现与创伤暴露或 PTSD 相关的显著全表观基因组 DNAm 改变 (FDR > .05)。从加权基因相关网络分析识别为模块的共甲基化位置与儿童或看护者的战争相关创伤经历或 PTSD 均无显著相关性。

结论：这些结果并未提供与战争相关创伤暴露或 PTSD 相关的 DNAm 模式改变的证据。

KEYWORDS:

• Burundian refugee families
• war trauma
• PTSD
• DNA methylation
• EWAS
• WGCNA

PALABRAS CLAVE:

• Familias de refugiados de Burundi
• trauma de guerra
• TEPT
• metilación del ADN
• EWAS
• WGCNA

关键词:

• 布隆迪难民家庭
• 战争创伤
• PTSD
• DNA 甲基化
• EWAS
• WGCNA

Acknowledgements

We thank all participating children and caregivers from Nyarugusu, Nduta, and Mtendeli. We are grateful to everyone involved in the data collection.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Health and safety

We confirm that all mandatory laboratory health and safety procedures have been complied with in the course of conducting the research reported in our paper.

Consent for publication

Each participant gave written informed consent that the results may be published for scientific purposes provided that the participant’s identity is not revealed and cannot be reconstructed.

Data availability statement

DNAm and phenotypic data are not publicly available due to de-anonymization risk but available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by Deutsche Forschungsgemeinschaft [grant number KU 2479/7-1]; Deutsche Forschungsgemeinschaft [grant number HE 8505/2-1]; North-South Cooperation Zurich University [grant number F-63212-13-01].