Epigenomic Predictors of PTSD and Traumatic Stress in an African American Cohort

项目总结 创伤后应激障碍(PTSD)是一种与压力相关的衰弱精神障碍， 影响非裔美国人(AA)。我们早期的工作确定了关键的社会逆境因素，包括孤独， 感觉到的歧视、累积的创伤、情感虐待和经济困难，这些因素结合在一起 糖皮质激素受体调节网络基因DNA甲基化可预测创伤后应激障碍 症状严重程度。而对白人和再障人群患创伤后应激障碍风险的研究表明， AAS在创伤暴露后患创伤后应激障碍的风险更高，但很少有研究明确 研究了导致再生障碍性贫血人群不同风险的社会环境因素。人口内 研究有可能揭示最终导致创伤后应激障碍风险的种族/民族差异的暴露。 事实上，结构、心理社会和环境机制，如生活在不安全的环境和 暴露于歧视中，可能会导致再生障碍性贫血患者出现不同的创伤后应激障碍风险。我们之前的研究证实了这些 调查结果。然而，尚不清楚的是：(I)积极的社交暴露的潜在缓冲效应， 如社会支持和凝聚力，已被证明在减轻创伤后应激障碍风险方面发挥重要作用； 以及(Ii)外周表观遗传措施与创伤后应激障碍的目标器官--大脑的相关性程度。 外周表观基因组变异与中枢神经系统表观基因组研究进展 变异(这里称为脑相关表观基因组变异)是迫切需要的，以获得更深层次的机制 洞察受此心理健康状况影响的AA中与创伤后应激障碍相关的健康差异。因此， 此续订应用程序的总体目标是提供对社会背景的机械性洞察，无论是积极的还是 负性，影响与大脑相关的表观基因组变异，从而影响前瞻性的创伤后应激障碍和创伤性应激的风险， 以社区为基础的AA队列。为了实现这一目标，我们将利用公开可用的多组织数据集来 确定在大脑和血液中高度相关的表观基因组标记，并将我们建议的分析集中在 这些相关的测量使用现有的和新收集的表观基因组和基因表达数据 底特律社区健康研究(DNHS)队列。基因组数据将与DNHS调查数据配对， 其中包括对社会逆境、精神病理学以及社会支持和凝聚力的年度衡量。我们会 重点分析我们之前工作中涉及的社会逆境(孤独，感知 歧视、累积创伤、经济困难、情感虐待)和积极的社会曝光率 以前与创伤后应激障碍(社会支持和邻里社会凝聚力)有关。这项研究的结果将 提供更深入的特征，说明社交暴露，无论是积极的还是消极的，如何影响大脑相关 表观基因组学过程对美国少数族裔AAS应激相关精神病理学的影响 在创伤应激相关精神病理学方面存在显著健康差异的群体。

PROJECT SUMMARY Post-traumatic stress disorder (PTSD) is a debilitating stress-related mental disorder that disproportionately impacts African Americans (AAs). Our earlier work identified key social adversity factors, including loneliness, perceived discrimination, cumulative trauma, emotional maltreatment and financial difficulties that, in combination with DNA methylation in glucocorticoid receptor regulatory network genes, prospectively predicted PTSD symptom severity. While studies examining the risk of PTSD among white and AA populations have shown that AAs are at a higher risk of PTSD following traumatic exposure, there are few studies that have specifically examined the socioenvironmental factors that lead to differential risk within AA populations. Within-population studies have the potential to uncover exposures that ultimately lead to race/ethnic disparities in PTSD risk. Indeed, structural, psychosocial and environmental mechanisms, such as living in unsafe environments and exposure to discrimination, may contribute to differential PTSD risk in AAs. Our prior research confirms these findings. What remains unknown, however, are: (i) the potential buffering effects of positive social exposures, such as social support and cohesion, which have been shown to play an important role in mitigating risk of PTSD; and (ii) the extent to which peripheral epigenetic measures are relevant to the target organ of PTSD—the brain. Advances in the science of linking peripheral epigenomic variation to central nervous system (CNS) epigenomic variation (herein called brain-related epigenomic variation) is urgently needed in order to gain deeper mechanistic insight into PTSD-related health disparities among AAs affected by this mental health condition. Therefore, the overall goal of this renewal application is to provide mechanistic insight into how social context, both positive and negative, affects brain-related epigenomic variation to impact risk of PTSD and traumatic stress in a prospective, community-based cohort of AAs. To achieve this goal, we will leverage publicly available, multi-tissue datasets to identify epigenomic markers that are highly correlated in brain and blood, and focus our proposed analyses on these correlated measures using existing and newly collected epigenomic and gene expression data from the Detroit Neighborhood Health Study (DNHS) cohort. The genomic data will be paired with DNHS survey data, which includes annual measures of social adversity, psychopathology, and social support and cohesion. We will focus analyses on social adversities previously implicated in our earlier work (loneliness, perceived discrimination, cumulative trauma, financial difficulties, emotional mistreatment) and positive social exposures previously implicated in PTSD (social support and neighborhood social cohesion). Results from this study will provide a deeper characterization of how social exposures, both positive and negative, influence brain-related epigenomic processes to impact stress-related psychopathology among AAs, an under-studied U.S. minority group with substantial health disparities in traumatic-stress related psychopathology.