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.

项目概要 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原因。 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 此外，个体的遗传倾向会增加或降低死亡风险。 这些条件可改变的活动和睡眠行为与遗传背景相结合的程度。 对于心血管风险的影响尚不清楚，这是一个重要的知识差距，因为当代。 身体活动建议不考虑遗传变异性。 提供来自可穿戴设备、全基因组的长期活动和睡眠数据的独特组合 这些数据源提供了机会。 我们了解行为如何与遗传因素相互作用从而导致疾病风险。 增加体力活动和改善睡眠对于减轻过度的遗传风险是必要的。 活动和睡眠持续时间和质量可以通过现在广泛使用的可穿戴设备进行量化和跟踪 这些设备能够高质量、纵向地收集这些措施，以便整合以提供信息。 遗传风险是心血管疾病的重要影响因素，也是导致心血管疾病的重要因素。 在量化可改变行为的作用时要考虑遗传背景代表的风险底线。 目前尚不清楚哪些行为和环境相互作用来确定疾病的发作和严重程度。 身体活动和睡眠等行为可能需要在多大程度上根据特定的基因进行调整 在使用“我们所有人”数据的初步工作中，我们进行了全表型研究。 步数与慢性疾病发生率之间的关联研究超过 590 万。 人日监测、心血管危险因素（肥胖、糖尿病、高血压和重度抑郁症） 在 1,700 种表型中出现的与较低步数最密切相关的表型。 扩展我们的工作来衡量潜在的遗传风险以及活动和睡眠模式对 目标 1 将量化遗传风险和体力活动对改变事件的相互作用。 使用肥胖、高血压、血脂异常、糖尿病和心血管疾病的多基因风险评分来评估心血管危险因素 次要分析将检查遗传风险对心血管结局的影响。 评估睡眠时间对心血管事件危险因素的影响，无论是否整合 我们的调查团队拥有独特的资格，可以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。 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 这项工作的研究和使用 Fitbit 数据将为个性化迈出第一步。 结合遗传背景的活动和睡眠指导。