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

战争和冲突相关创伤的表观遗传特征——对非洲难民家庭的研究

• 批准号: 451968036
• 负责人: Professor Dr. Tobias Hecker
• 金额: --
• 依托单位: Institut für interdisziplinäre Konflikt- und Gewaltforschung (IKG)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/451968036?language=en
• 关键词: Epigenetic; signatures; war; conflict; related

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.

全世界的难民人数已超过2 500万人。一般估计认为，50%以上逃离武装冲突的难民受到心理健康问题的影响，如创伤后应激障碍。了解行为脆弱性的心理和生物基础以及对创伤压力的复原力是公共卫生的优先事项，因为这将有助于制定有针对性的预防战略和治疗干预措施。有大量证据表明，遭受战争和冲突相关创伤与精神病理学风险增加之间存在联系。然而，创伤暴露后PTSD的患病率存在显著的差异。表观遗传过程被认为是一种介导机制。然而，将创伤暴露和/或创伤相关的精神病理学与特定的表观遗传改变联系起来的令人信服的人类证据仍然很少。这部分是由于设计限制以及大多数研究迄今为止都集中在基因覆盖率低的候选基因上，这可能会错过重要的差异甲基化基因组区域。为数不多的表观基因组范围的研究规模较小，因此检测效果的能力不足。因此，到目前为止，还没有明确的表观遗传PTSD特征。 在拟议的项目中，我们将通过调查一个具有良好动力（n > 600）和良好特征的难民家庭样本来解决这些局限性，这些难民家庭暴露于多重严重创伤，他们使用最先进的基于阵列的技术重新安置在难民营中，以探索整个基因组中与PTSD症状相关的改变，然后验证最高命中率。为此目的，我们已经成功地从位于坦桑尼亚的三个大型难民营中的布隆迪难民家庭三合会（父亲、母亲和一个孩子）的代表性样本中收集了数据。我们的样本特别适合于研究创伤经历，创伤相关疾病和潜在的表观遗传机制之间的相互作用，因为样本在创伤经历以及种族和遗传背景以及目前的生活状况方面是同质的，并且以战争和冲突相关暴力的形式显示出非常高的创伤暴露水平。 在拟议的项目中，我们的目标是确定PTSD相关的DNA甲基化改变，以区分与战争相关的创伤暴露后发展PTSD的个体和具有相同暴露的未受影响的个体。我们进一步的目的是表明创伤负荷与DNA甲基化模式有关。最后，我们的目标是证明DNA甲基化在创伤暴露和PTSD风险之间的关联中的介导作用。此外，我们的目标是使用现有的验证样本来确认我们的发现。