Leveraging omics data to understand sleep health and its consequences among diverse Hispanics/Latinos

项目摘要 拉美裔是美国增长最快的人口群体，预计将占美国的24% 到2060年人口。拉丁美洲人的健康差距率很高，包括高负担， 心血管危险因素、糖尿病（DM）、不受控制的高血压（HTN）、肥胖和阿尔茨海默病 疾病和血管性痴呆。西班牙裔社区健康研究/拉丁裔研究（HCHS/SOL）是一项 2004年建立的纵向队列研究，跟踪了来自四个地理区域的约16，500名美国拉丁美洲人， 来自多个拉丁美洲背景（墨西哥，南美，中美洲，古巴，多米尼加， 波多黎各）。我们在基线检查期间监督睡眠测量的收集和分析。沿着 我们的同事，我们确定了睡眠障碍的高患病率，其频率因社会和 行为因素和拉丁裔背景，并与事件DM，HTN和认知能力下降， 损伤 本课题将采用综合性、多学科的研究方法，研究生物学机制， 在不同的拉丁美洲人中，导致与睡眠健康相关的糖尿病、高血压和认知能力下降的风险。一是 确定与睡眠表型相关的甲基化和代谢组学指标，并对其进行表征 从生理上来说我们将把其中一些措施与可改变的生活方式和社会文化措施联系起来。二是 通过结合多个标记物的信息，开发睡眠的代谢组学和甲基化生物标志物。 我们将研究这些生物标志物与事件结局（DM、HTN、认知能力下降和 损伤）。第三，我们将评估睡眠表型对改变糖尿病、高血压、 和认知结果，使用基因与睡眠相互作用分析， 结果。我们还将进行多组学分析，综合多种组学措施，以了解 生物途径。最后，我们将应用因果分析来量化事故风险的潜在降低 糖尿病、高血压、认知功能下降和睡眠表型潜在干预后的损害， 代谢组学和遗传途径可以被阻断的假设。我们将估计这些影响， 在拉丁裔背景下的聚集。我们的工作将导致公共卫生干预措施的发展， 社区级别（例如，解决改善睡眠健康的策略）和个人层面： 例如，根据遗传学，确定谁将从改善睡眠中受益最多 或代谢组学图谱。

PROJECT SUMMARY Hispanics/Latinos are the fastest growing demographic group in the U.S., expected to comprise 24% of the US population by 2060. Latinos experience high rates of health disparities, including a high burden of cardiovascular risk factors, diabetes mellitus (DM), uncontrolled hypertension (HTN), obesity, and Alzheimer’s Disease and vascular dementias. The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a longitudinal cohort study established in 2004, following ~16,500 US Latinos from four geographic areas and from multiple Latino backgrounds (Mexican, South American, Central American, Cuban, Dominican, and Puerto Rican). We oversaw the collection and analysis of sleep measures during its baseline exam. Along with our colleagues, we identified a high prevalence of sleep disorders which varied in frequency by social and behavioral factors and Latino background, and associated with incident DM, HTN, and cognitive decline and impairment. In this project we will apply an integrative and multi-disciplinary research to study biological mechanisms that result in sleep health-related risk of DM, HTN, and cognitive decline across diverse Latinos. First, we will identify methylation and metabolomics measures associated with sleep phenotypes, and characterize them biologically. We will link some of them to modifiable lifestyle and sociocultural measures. Second, we will develop metabolomics and methylation biomarkers of sleep by combining information across multiple makers. We will study the association such biomarkers with incident outcomes (DM, HTN, cognitive decline and impairment). Third, we will estimate the effect of sleep phenotypes on modifying genetic risks for DM, HTN, and cognitive outcomes using a gene-by-sleep interaction analysis with polygenic risk scores for each outcome. We will also perform multi-omics analyses synthesizing multiple omics measures to understand biological pathways. Finally, we will apply causal analysis to quantify the potential reduction in risks of incident DM, HTN, and cognitive decline and impairment following potential intervention on sleep phenotypes, under the assumption that metabolomics and genetic pathways can be blocked. We will estimate these effects in aggregate and across Latino backgrounds. Our work will lead to development of public health interventions at the community level (e.g., addressing strategies to improve sleep health) and at the personal level: by identifying individuals who will benefit most from improving their sleep, for example, according to their genetics or metabolomics profile.