Epigenetic signatures of war and conflict-related trauma - a study of refugee families in Africa

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The number of refugees in the world has reached more than 25 million people. General estimates hold that more than 50% of the refugees who have fled armed conflicts are affected by mental health problems, such as posttraumatic stress disorder (PTSD). Understanding the psychological and biological underpinnings of behavioral vulnerability and resilience to traumatic stress is a public health priority, as it would facilitate the development of targeted preventative strategies and therapeutic interventions. There is extensive evidence showing a link between exposure to war- and conflict-related trauma and increased risk for psychopathology. However, there exists significant variability in PTSD prevalence following trauma exposure. Epigenetic processes have been proposed as a mediating mechanism. However, compelling human evidence linking trauma exposure and/or trauma-related psychopathology to specific epigenetic alterations remains sparse. This is partly due to design limitations and the fact that the majority of studies has so far focused on candidate genes with low coverage across genes, which might miss important differentially methylated genomic regions. The few epigenome-wide studies were small and thus underpowered to detect effects. Thus, no clear picture of an epigenetic PTSD signature has emerged so far. In the proposed project, we will address these limitations by investigating a well-powered (n > 600) and well-characterized sample of refugee families exposed to multiple severe trauma who have resettled in refugee camps using state-of-the-art array-based technology to explore PTSD symptom related alterations across the genome, followed by validation of top hits. For this purpose, we have already successfully collected data from a representative sample of Burundian refugee family triads (father, mother, and one child) in three large refugee camps that are located in Tanzania. Our sample is particularly suitable for studying the interplay of traumatic experiences, trauma-related disorders, and potential epigenetic mechanisms because the sample is homogeneous in terms of their traumatic experiences as well as their ethnic and genetic background and current living situation, and shows a very high level of trauma exposure in the form of war- and conflict-related violence. In the proposed project, we aim to identify PTSD-associated alterations of DNA methylation that distinguish between individuals who developed PTSD following war-related trauma exposure and unaffected individuals with the same exposure. We further aim to show that trauma load is related to DNA methylation patterns. Lastly, we aim to demonstrate the mediating role of DNA methylation in the association between trauma exposure and PTSD risk. In addition, we aim to confirm our findings using existing validation samples.