Impact of Physical Activity, Sleep, and Genetic Background on Cardiovascular Risk in the All of Us Program

“我们所有人”计划中体力活动、睡眠和遗传背景对心血管风险的影响

• 批准号: 10795533
• 负责人: Evan L Brittain
• 金额: $ 21.88万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10795533
• 关键词: Address; All of Us Research Program; Atrial Fibrillation; Behavior; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chronic Disease; Clinical; Clinical Data; Collection; Cox Proportional Hazards Models; Data; Data Sources; Devices; Diabetes Mellitus; Disease; Dyslipidemias; Electronic Health Record; Environment; Floor; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genome; Genomics; Health; Heart failure; Hypertension; Incidence; Individual; Knowledge; Major Depressive Disorder; Measures; Mental Depression; Modeling; Monitor; Morbidity - disease rate; Myocardial Infarction; Nature; Obesity; Onset of illness; Outcome; Patient-Focused Outcomes; Peripheral arterial disease; Persons; Phenotype; Physical activity; Population; Qualifying; Recommendation; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Severity of illness; Sleep; Sleep Disorders; Source; Stroke; Testing; Time; Work; burden of illness; cardiovascular disorder risk; cardiovascular risk factor; care seeking; cohort; disorder risk; fitbit; genome sequencing; genomic data; high risk; human disease; improved; improvement on sleep; modifiable behavior; mortality; phenome; polygenic risk score; secondary analysis; sleep behavior; sleep pattern; wearable device; whole genome

PROJECT SUMMARY Cardiovascular disease and its risk factors are major contributors to health burden and early death. Physical activity and sleep patterns are important behaviors that are causally tied to cardiovascular morbidity and mortality. Additionally, an individual’s genetic predisposition contributes to either increased or decreased risk of these conditions. The extent to which modifiable activity and sleep behaviors combine with genetic background to influence cardiovascular risk is not known. This is an important knowledge gap because contemporary physical activity recommendations do not account for genetic variability. The All of Us Research Program offers a unique combination of long-term activity and sleep data from wearable devices, whole-genome sequencing, and clinical outcomes from patients seeking care. These data sources provide an opportunity to understand how behaviors interact with genetic factors to contribute to incident disease risk. We hypothesize that increased physical activity and improved sleep will be necessary to mitigate excess genetic risk. Physical activity and sleep duration and quality can be quantified and tracked by wearables that are now widely used by the public. These devices enable high quality, longitudinal collection of these measures to integrate to inform impact on disease. Genetic risk is a significant contributor to cardiovascular disease and an important factor to consider when quantifying the role of modifiable behaviors. Genetic background represents a risk floor upon which behavior and environment interact to determine disease onset and severity. It is currently unclear to what degree behaviors such as physical activity and sleep might need to be adjusted to the specific genetic background of the individual. In preliminary work using All of Us data, we performed a phenome-wide association study of the association between step counts and incident chronic disease. Over 5.9 million person-days of monitoring, cardiovascular risk factors (obesity, diabetes, hypertension, and major depression) emerged among 1,700 phenotypes as most strongly associated with lower step counts. We now propose to extend our work to measure the impact of underlying genetic risk and activity and sleep patterns on cardiovascular risk. Aim 1 will quantify the interaction of genetic risk and physical activity on modifying incident cardiovascular risk factors using polygenic risk scores for obesity, hypertension, dyslipidemia, diabetes, and depression. Secondary analyses will examine the impact of genetic risk on cardiovascular outcomes. Aim 2 will assess the impact of sleep duration on incident cardiovascular risk factors with and without integration of genetic risk. Our investigative team is uniquely qualified to maximally leverage the available sources of data in All of Us to quantify the combined impact of sleep, activity, and genetics on cardiovascular risk. We have collective expertise in cardiovascular disease, genomic analysis, electronic health record cohorts, sleep research, and use of Fitbit data. The results of this work will provide an initial step toward personalization of activity and sleep guidance that incorporates genetic background.

项目摘要 心血管疾病及其危险因素是伯宁健康和早期死亡的主要因素。身体的 活动和睡眠方式是重要行为，有时与心血管发病率相关 死亡。此外，一个人的遗传易感性有助于增加或降低 这些条件。可修改活动和睡眠行为与遗传背景结合的程度 影响心血管风险尚不清楚。这是一个重要的知识差距，因为当代 体育活动建议不考虑遗传变异性。我们所有的研究计划 提供了来自可穿戴设备的长期活动和睡眠数据的独特组合 测序以及寻求护理患者的临床结果。这些数据源为 了解行为如何与遗传因素相互作用以促进入射疾病风险。我们假设 需要增加体育锻炼和改善的睡眠，以减轻过多的遗传风险。身体的 活动，睡眠持续时间和质量可以通过可穿戴设备来量化和跟踪，这些可穿戴设备现在已广泛使用 公众。这些设备使这些措施的高质量，纵向集合以通知 对疾病的影响。遗传风险是心血管疾病的重要原因，也是对 量化可修改行为的作用时考虑。遗传背景代表风险地板 哪种行为和环境相互作用以确定疾病的发作和严重程度。目前尚不清楚 可能需要将诸如体育锻炼和睡眠之类的程度行为调整为特定的通用性 个人的背景。在使用我们所有数据的初步工作中，我们进行了整个现象 协会研究步骤计数与入射慢性疾病之间的关联。超过590万 监测的人日，心血管危险因素（肥胖，糖尿病，高血压和重度抑郁症） 在1,700个表型中出现，因为与较低的步骤计数最密切相关。我们现在建议 扩展我们的工作，以衡量潜在的遗传风险和活动和睡眠模式对 心血管风险。 AIM 1将量化遗传风险和体育锻炼的相互作用 使用多基因风险评分的心血管危险因素用于肥胖，高血压，血脂异常，糖尿病和 沮丧。次级分析将检查遗传风险对心血管结局的影响。 AIM 2意志 评估睡眠持续时间对事件心血管危险因素的影响，没有和不整合 遗传风险。我们的调查团队具有独特的资格，可以最大程度地利用可用的数据来源 我们所有人都量化睡眠，活动和遗传学对心血管风险的综合影响。我们有 心血管疾病，基因组分析，电子健康记录队列，睡眠方面的集体专业知识 研究和使用FITBIT数据。这项工作的结果将为个性化的第一步提供 活动和睡眠指导融合了遗传背景。