Social Circumstances and Epigenomics Promoting Health in Three Countries

该项目提出了一套综合的目标，并对来自三个国家的现有社会和表观遗传数据进行了分析 健康和退休研究家庭中的国家老龄化研究(美国健康和退休研究 (HRS)，北爱尔兰老龄化纵向研究队列(尼古拉)和爱尔兰纵向 老化研究(Tilda)；对现有样本进行分析，以产生三个样本的纵向表观遗传学数据 还提出了国家。基于这些数据的比较分析将解决以下核心问题 童年和成年期的生活环境如何影响表观遗传变化，以及不同的历史和 这些国家的生命周期暴露可能会导致不同的关联模式。该项目还将 研究表观遗传变化如何反过来与50岁后的健康相关。该提案提交于 对美国-爱尔兰研究和发展伙伴关系的回应，这是一项独特的研究倡议，涉及 来自美国(US)、爱尔兰共和国(ROFI)和北爱尔兰(NI)的资助机构。 向这三个国家中的每个国家提交提案，并为每个国家的参与申请资金 来自其各自的拨款机构(例如，美国国家卫生研究院)；仅由国家卫生研究院对所有三个基于 关于这项提议。该项目将考察终身社会、经济、心理、 环境和行为环境，以及与衰老和健康有关的表观遗传标记，以及 随后的健康状况。表观遗传修饰是衰老的“标志”之一，即一种潜在的生理变化 可以加速或延缓与衰老相关的健康结果的变化。更快的衰老是中国人的特征 不利的社会环境和表观遗传变化，特别是DNA甲基化(DNaM)，似乎是 尤其是在早年和晚年都受到不利的社会环境的影响。这个项目将是 在评估各种社会环境，即低教育水平和低收入、少数族裔 团体成员，不良童年经历，成人创伤，危险健康行为，心理状态， 和慢性应激，在三个不同的国家与表观遗传标记有关，略有不同 在不同的卫生政策制度下运作的历史、社会和行为特征--允许 对于假设影响相似的复制和假设它们的差异 不同(例如，风险特征由SES以不同的模式表示)。申请者的安置是独一无二的 与他们的资源一起探索整个生命过程中的社会经济经历如何改变表观遗传学特征 影响健康结果，如生物调节失调、虚弱、残疾、慢性病和早产 死亡率。从研究一开始，就统一了三个数据集以收集信息 旨在鼓励比较分析。它们已在调查信息中进行了协调 以及这三个国家的表观遗传学数据的发展。每个国家都有很强的独立研究能力 团队将独特的专业知识和资源以及协作历史带到这个协作提案中。

This project proposes an integrated set of aims and analyses of existing social and epigenetic data from three national studies of aging in the family of Health and Retirement studies (the US Health and Retirement Study (HRS), the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA), and the Irish Longitudinal Study of Aging (TILDA)); assays of existing samples to produce longitudinal epigenetic data for the three countries are also proposed. Comparative analyses based on these data will address central questions about how life circumstances in both childhood and adulthood affect epigenetic change and how different historical and life-course exposures in these countries may result in differential patterns of associations. The project will also examine how epigenetic changes in turn are associated with health after age 50. The proposal is submitted in response to the US-Ireland Research and Development Partnership, a unique research initiative involving funding agencies from the United States (US), the Republic of Ireland (RofI), and Northern Ireland (NI). Proposals are submitted to each of the three countries with funding requested for each country's participation from their respective grant agency (e.g., US NIH); grant review is done only by NIH for all three projects based on this proposal. The project will examine the links between lifetime social, economic, psychological, environmental and behavioral circumstances, and epigenetic markers related to aging and health, and subsequent health. Epigenetic modification is one of the “hallmarks” of aging, i.e. an underlying physiological change that can speedup or delay aging-related health outcomes. Faster aging is characteristic of people in adverse social circumstances and epigenetic change, particularly DNA methylation (DNAm), appears to be especially influenced by adverse social circumstances, both at early ages and at later ages. This project will be unique in evaluating how a variety of social circumstances, i.e. low levels of education and income, minority group membership, adverse childhood experiences, adult traumas, risky health behaviors, psychological states, and chronic stress, are associated with epigenetic markers in three different countries, with somewhat different historical, social and behavioral characteristics which are operating in different health policy regimes – allowing for both replication where effects are hypothesized to be similar and differentiation where they are hypothesized to differ (e.g., where risk characteristics are differentially patterned by SES). The applicants are uniquely placed with their resources to explore how socioeconomic experiences across the life course alter epigenetic profiles to influence health outcomes such as biological dysregulation, frailty, disability, chronic disease, and premature mortality. The three data sets have been harmonized for information collection from the beginning of the studies and were designed to encourage comparative analysis. They have been harmonized in the survey information and the development of the epigenetic data in the three countries. Each country has strong independent research teams who bring unique expertise and resources and a history of collaboration to this collaborative proposal.