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异率很高，包括糖尿病的高负担 糖尿病（DM）、不受控制的高血压（HTN）、肥胖和阿尔茨海默病和血管性痴呆。 西班牙裔社区健康研究/拉丁裔研究（HCHS/SOL）是一项纵向队列研究， 2004年，来自四个地理区域和多种拉丁美洲背景的16,500名美国拉丁美洲人（墨西哥人， 南美洲、中美洲、古巴、多米尼加和波多黎各）。我们监督了收藏， HCHS/SOL基线检查期间的睡眠测量分析。沿着我们的同事，我们确定了一个 睡眠障碍患病率高，因社会和行为因素以及拉丁裔背景而异， 与糖尿病、高血压、认知功能下降和损害有关。 本项目将采用综合性和多学科的研究方法，研究生物机制， 在不同的拉丁美洲人中导致与睡眠相关的糖尿病、高血压和认知能力下降的风险。首先，我们将确定 与睡眠表型相关的甲基化和代谢组学测量，并在生物学上表征它们。 我们进一步确定了这些组学措施的一个子集，这些措施与可改变的生活方式和社会文化有关 措施第二，我们将结合代谢组学和甲基化生物标志物来开发睡眠。 多个标记的信息。我们将研究这些生物标志物与事件结果的关系 (DM HTN，认知下降和损伤）。第三，我们将评估睡眠表型对 使用基因-睡眠相互作用分析， 每个结果的多基因风险评分。我们还将进行多组学分析， 了解生物学途径的措施。最后，我们将应用因果分析来量化潜在的 潜在干预后，DM、HTN和认知功能下降和受损的风险降低 睡眠表型，假设代谢组学和遗传途径可以被阻断。我们将 估计这些影响的总体和跨拉丁美洲背景。我们的工作将导致 社区的公共卫生干预措施-例如，在墨西哥裔拉丁美洲人中）和患者水平， 个体（例如，基于特定的遗传或代谢组学特征），谁将从改善 他们的睡眠

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 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 multiple Latino backgrounds (Mexican, South American, Central American, Cuban, Dominican, and Puerto Rican). We oversaw the collection and analysis of sleep measures during the HCHS/SOL baseline exam. Along with our colleagues, we identified a high prevalence of sleep disorders which varied by social and behavioral factors and Latino background, and were associated with incident DM, HTN, and cognitive decline and impairment. This project will apply integrative and multi-disciplinary research methods to study biological mechanisms that result in the sleep-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 further identify a subset of these omics measures that are linked to modifiable lifestyle and sociocultural measures. Second, we will develop metabolomics and methylation biomarkers of sleep by combining information across multiple markers. We will study the association of 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 the development of public health interventions at the community-(e.g., in Latinos of Mexican origin) and patient-level by identifying individuals (e.g., based on specific genetic or metabolomic profiles) who would benefit most from improving their sleep.