Community Driven Approach to Mitigate COVID 19 Disparities in Hawaii's Vulnerable Populations

夏威夷原住民和太平洋岛民(NHS/PI)的患病率高得不成比例 和更早出现心脏代谢健康结果，包括2型糖尿病(DM)和 心血管疾病(CVD)，而不是其他种族/民族群体。这些健康差异可能是由于 塑造个人健康行为的社会环境(如营养、体育活动和教育)和 可能介导基因-环境相互作用的生理反应。社会的有害影响 环境可能包括全身炎症的增加，这是心脏代谢性疾病的一个特征， 免疫系统的单核细胞起着主要作用。我们观察到社区的社会环境 与脆弱人群中的炎症有关。此外，其他研究表明，单核细胞介导的 炎症导致靶细胞胰岛素抵抗和心脏代谢风险增加 疾病。表观遗传机制，包括DNA甲基化，调节促炎转录 单核细胞中的基因。我们假设邻里的社会环境导致DNA的全球变化 免疫细胞甲基化状态与心脏代谢性疾病风险相关。在我们的工作中，我们观察到 致炎基因的DNA甲基化和基因表达状态在全基因组范围内的显著变化 与糖尿病患者单核细胞炎症活动和血糖控制相关的基因，以及强大的DNA 单核细胞胰岛素抵抗与心血管疾病风险相关的甲基组特征。总而言之，这些数据 提示心脏代谢性疾病可能在一定程度上是由社会环境引起的 单核细胞炎症状态下的表观基因组图景。在这项研究中，我们将解决 邻里社会环境是否影响不同地区单核细胞的表观基因组变异性 夏威夷的少数民族人群，并解释了心脏代谢健康差异，特别是#年的糖尿病 NHS/PI。为此，我们建议将详细的个人层面的健康行为、临床/免疫学、 遗传和单核细胞特异性表观基因组数据与邻居级别的社会环境数据来自我们的 多民族队列研究(MEC)通过对可见保存的细胞进行基于群体的前瞻性研究，我们 将有一个前所未有的机会来研究表观基因组信息在 预测20年随访期间发生的临床诊断的糖尿病。正如NHS/PI所做的那样 DM的发病率高得不成比例，我们预计免疫表观遗传特征的频率会增加 对糖尿病结果的预测，这将为健康差距的病因提供新的见解。因此， 我们相信，我们的社会表观多种族研究符合FOA推动科学发展的总体目标 关注健康差异的表观基因组学，扩展理解表观遗传机制的方法 通过哪些社会因素导致影响健康差距的生物学变化，并促进表观遗传学 更好地诊断弱势群体的疾病风险或复原力的研究。

Native Hawaiians and Pacific Islanders (NHs/PIs) experience a disproportionately higher prevalence and earlier onset of cardiometabolic health outcomes, including Type-2 diabetes mellitus (DM) and cardiovascular disease (CVD), than other racial/ethnic groups. These health disparities may result from the social environment shaping an individual’s health behaviors (e.g. nutrition, physical activity, and education) and physiological responses that may mediate gene-environment interactions. The detrimental effects of social environments may include an increase in systemic inflammation, a hallmark of cardiometabolic diseases where monocytes of the immune system play a major role. We observed neighborhood social environments that associated with inflammation in vulnerable populations. Additionally, other studies show that monocyte-mediated inflammation leads to insulin resistance in target cells and heightened risk of cardiometabolic diseases. Epigenetic mechanisms, including DNA methylation, regulate transcription of pro-inflammatory genes in monocytes. We posit that neighborhood social environment leads to global changes in DNA methylation states in immune cells associated with cardiometabolic disease risk. In our work, we observed significant genome-wide changes to DNA methylation and gene expression states of pro-inflammatory genes that associated with monocyte inflammatory activity and glycemic control in DM patients, and a robust DNA methylomic signature of insulin resistance in monocytes that correlated with CVD risk. Together, these data suggest that cardiometabolic diseases may in part result from social environment-induced changes to the epigenomic landscape in monocytes underlying their inflammatory states. In this study, we will address whether the neighborhood social environment impacts epigenomic variability in monocytes across different ethnic populations in Hawaii and account for cardiometabolic health disparities, specifically to that of DM in NHs/PIs. To do so, we propose to integrate detailed individual-level health behavior, clinical/immunologic, genetic, and monocyte-specific epigenomic data with neighborhood-level social environment data from our Multiethnic Cohort Study (MEC). By using a population-based prospective study with viably preserved cells, we will have an unprecedented opportunity to examine the translational utility of epigenomic information in predicting clinically diagnosed DM that occurred during a 20-year follow-up. As NHs/PIs have disproportionately high rates of DM, we anticipate an increased frequency of an immunoepigenetic signature predictive of DM outcomes, which would provide novel insight into the etiology of health disparities. Therefore, we believe our social epigenomic multiethnic study meets the overall goals of this FOA to advance the science of epigenomics focused on health disparities, expand approaches for understanding epigenetic mechanisms by which social factors lead to biological changes that affect health disparities, and promote epigenetics research to better diagnose disease risk or resiliency among disadvantaged populations.