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造成健康负担和过早死亡的主要因素。物理 活动和睡眠模式是与心血管疾病发病率有因果关系的重要行为， mortality.此外，个体的遗传易感性有助于增加或减少以下风险： 了以下条件可改变的活动和睡眠行为联合收割机与遗传背景结合的程度 影响心血管风险的因素尚不清楚。这是一个重要的知识差距，因为当代 身体活动建议没有考虑到遗传变异。All of Us研究计划 提供来自可穿戴设备的长期活动和睡眠数据的独特组合， 测序和寻求护理的患者的临床结果。这些数据源提供了机会， 了解行为如何与遗传因素相互作用，从而导致疾病风险。我们假设 增加身体活动和改善睡眠是减轻过度遗传风险的必要条件。物理 活动和睡眠持续时间和质量可以通过现在被广泛使用的可穿戴设备来量化和跟踪。 公众这些设备能够高质量地纵向收集这些措施，以整合信息， 对疾病的影响。遗传风险是心血管疾病的一个重要因素， 在量化可修改行为的作用时要考虑。遗传背景代表了一个风险底线， 哪些行为和环境相互作用决定了疾病的发作和严重程度。目前尚不清楚， 什么程度的行为，如身体活动和睡眠，可能需要调整到特定的遗传 个人的背景。在使用All of Us数据的初步工作中，我们进行了全现象范围的 步数与慢性病发病率之间的关联研究。超过590万 监测人-天，心血管风险因素（肥胖、糖尿病、高血压和重度抑郁症） 在1,700种表型中，与较低的步数最密切相关。我们现建议 将我们的工作扩展到测量潜在的遗传风险和活动以及睡眠模式对 心血管风险。目标1将量化遗传风险和身体活动对修改事件的相互作用 使用肥胖、高血压、血脂异常、糖尿病和糖尿病的多基因风险评分， 萧条次要分析将检查遗传风险对心血管结局的影响。目标2将 评估睡眠时间对心血管危险因素的影响， 遗传风险我们的调查团队是唯一有资格最大限度地利用现有的数据来源， 我们所有人都在量化睡眠，活动和遗传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提供第一步， 结合遗传背景的活动和睡眠指导。