Researching Epigenetics, Weathering, Aging & Residential Disadvantage (REWARD)

项目摘要 这两个非洲裔美国人生活在隔离的社会经济弱势城市社区， 农村地区资源贫乏的居民过早死亡率很高， 心血管疾病、癌症和其他不良健康状况的负担。解释了 物质和社会不利的经历体现并随后表现在种族和 地理上的健康差异是研究、政策和实践的关键挑战。虽然持续的社会 众所周知，不利因素会形成健康差距，这一过程背后的生物机制- 被称为风化作用-仍有待阐明。最近发现的生物老化的不同速度 （使用DNA甲基化测量）表明， 表观基因组可能在风化过程中起关键作用。表观遗传标记也与已知的 多种慢性病的差异。研究表观遗传学，风化，老化和住宅 缺点（奖励）研究将促进我们对DNA甲基化作为一种表观遗传学的理解。 一种将社会、经济和地理劣势与加速衰老和表型联系起来的机制， 炎症和心脏代谢疾病。我们的目标是确定 劣势-包括个人特征（如种族认同、社会经济地位和 相关的歧视经历），以及邻里水平的背景特征（例如， 集中的贫困、种族隔离和农村隔离）通过表观遗传形成健康差距 机制等我们假设，早期生活和累积的个人和环境的不利因素预测DNA 甲基化模式，创造了风化的生物特征，有助于加速生物降解。 易受伤害人群中的衰老、炎症和心脏代谢疾病。很少有研究拥有时间 后续行动的范围，地理多样性，以及种族隔离和农村隔离的极端需要测试 假设个人和邻里水平的不利因素在整个生命过程中有助于 逆境的生物学特征REWARD使用来自正在进行的基于人口的 威斯康星州--一个以城市种族隔离和农村隔离等明显不平等而闻名的州。 使用850 K Infinium EPIC芯片阵列，我们将分析1400名参与者的全血DNA和血清 在威斯康星州（SHOW）的健康调查中，一项正在进行的、特征良好的、以人群为基础的队列研究， 威斯康星州的成年人。这个多元化的团队包括来自威斯康星大学麦迪逊分校的科学家， 医学和公共卫生和社会学系，以及一个领先的生物人类学家从 西北大学和加州大学洛杉矶分校的遗传学家和生物统计学家谁开发了霍瓦特 表观遗传时钟REWARD研究将遗传、社会人口统计学、行为和 邻里水平的数据将使我们的多学科研究团队提供新的见解（目标1） 检查跨多个不利领域的DNA甲基化特征的差异;（目标2） 研究将加速生物老化与功能基因表达联系起来的表观遗传机制， 炎症和心脏代谢疾病;以及（目的3）表征整个 衰老和疾病的表观遗传标记的纵向变化。这项研究的结果将 强调人类对逆境的生物反应的可变性，并为预防和治疗 与年龄有关的疾病，减少和减轻健康差距，改善老龄人口的健康。

PROJECT SUMMARY Both African Americans living in segregated socioeconomically disadvantaged urban neighborhoods and resource-poor residents of rural areas experience high rates of premature mortality and a disproportionate burden of cardiovascular disease, cancer, and other adverse health conditions. Explaining how varied experiences of material and social disadvantage become embodied and subsequently manifest in racial and geographic health disparities is the key challenge for research, policy, and practice. While persistent social disadvantage is known to shape health disparities, the biological mechanisms that underlie this process – known as weathering – remain to be elucidated. The recent discovery of differential rates of biological aging (measured using DNA methylation) across subpopulations facing early life disadvantage suggest that the epigenome may play a key role in weathering. Epigenetic markers have also been linked with known disparities in multiple chronic conditions. The Researching Epigenetics, Weathering, Aging & Residential Disadvantage (REWARD) study will advance our understanding of DNA methylation as one epigenetic mechanism linking social, economic, and geographic disadvantage with accelerated aging and phenotypes of inflammation and cardio-metabolic diseases. Our goal is to determine how different dimensions of disadvantage – including individual characteristics (e.g. racial identification, socioeconomic status, and associated experiences of discrimination), and neighborhood-level contextual characteristics (e.g. concentrated poverty, racial segregation, and rural isolation) – shape health disparities through epigenetic mechanisms. We hypothesize that early-life and cumulative personal and contextual disadvantage predict DNA methylation patterns, creating biological signatures of weathering that contribute to accelerated biological aging, inflammation, and cardiometabolic disease in vulnerable populations. Few studies possess the temporal range of follow-up, geographic diversity, and extremes in racial segregation and rural isolation needed to test the hypothesis that individual and neighborhood-level disadvantage across the life course contribute to biological signatures of adversity. REWARD fills these gaps using rich data from an ongoing population based cohort in Wisconsin -- a state known for stark disparities including urban racial segregation and rural isolation. Using the 850K Infinium EPIC Chip array, we will analyze whole blood DNA and serum from 1400 participants in the Survey of the Health of Wisconsin (SHOW), an ongoing, well-characterized, population-based cohort of Wisconsin adults. The diverse team includes scientists from the University of Wisconsin-Madison’s School of Medicine and Public Health and Department of Sociology, as well as a leading biological anthropologist from Northwestern University and the UCLA-based geneticist and biostatistician who developed the Horvath epigenetic clock. The REWARD Study’s unique combination of genetic, socio-demographic, behavioral, and neighborhood-level data will allow our multidisciplinary research team to provide new insights by (Aim 1) examining differences in DNA methylation signatures across multiple domains of disadvantage; (Aim 2) investigating the epigenetic mechanisms linking accelerated biological aging with functional gene expression, inflammation, and cardio-metabolic disease; and (Aim 3) characterizing the impact of disadvantage across the life course on longitudinal changes in epigenetic markers of aging and disease. Findings from this research will highlight the variability in human biological response to adversity and inform interventions to prevent and treat age-related disease, reduce and mitigate health disparities, and improve the health of aging populations.