Cardiovascular Disease Risk Factors, Cardiovascular Disease Risk Prediction, and Genetics in the Million Veteran Program

百万退伍军人计划中的心血管疾病危险因素、心血管疾病风险预测和遗传学

• 批准号: 10421253
• 负责人: PETER WYMAN WILSON
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10421253
• 关键词: Address; African American population; Age; Alcohol consumption; Ambulatory Care; American; Atherosclerosis; Atrial Fibrillation; Bioinformatics; Blood Cells; Blood Pressure; Body mass index; Cardiovascular Diseases; Cessation of life; Cohort Studies; Complete Blood Count; Coronary Artery Bypass; Coronary heart disease; Data; Data Element; Data Sources; Databases; Development; Diabetes Mellitus; Diet; Disease Outcome; Electronic Health Record; Elements; Enrollment; Environment; Ethnic Origin; European; Event; Food; Fostering; Frequencies; Funding; Future; Genes; Genetic; Genetic Risk; Genetic Variation; Glycosylated hemoglobin A; Health; Heart Valve Diseases; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Hispanic Americans; Incidence; Inflammatory; Inflammatory Arthritis; Intake; Investigation; LDL Cholesterol Lipoproteins; Link; Lipids; Longitudinal prospective study; Low-Density Lipoproteins; Measurement; Measures; Medicare; Methods; Myocardial Infarction; Nutrient; Obstructive Sleep Apnea; Outcome; Outpatients; Participant; Patient Self-Report; Pharmacological Treatment; Phenotype; Physical activity; Population Group; Prevalence; Primary Health Care; Process; Questionnaires; Race; Recording of previous events; Recurrence; Research; Research Design; Risk; Risk Factors; Role; Smoking; Stroke; Subgroup; Techniques; Testing; Time; Triglycerides; Variant; Vascular Diseases; Veterans; Visit; White Blood Cell Count procedure; Work; adjudication; base; blood glucose regulation; cardiovascular disorder risk; cardiovascular effects; cardiovascular risk factor; clinical diagnosis; clinical risk; cohort; genetic association; genetic risk factor; genetic variant; genome wide association study; healthy aging; heart disease risk; indexing; percutaneous coronary intervention; post stroke; precision medicine; predictive modeling; professional atmosphere; programs; prospective; rare variant; risk prediction; sex; structural heart disease; survival outcome; survivorship; trait; treatment effect; valvular stenosis; virtual

Cardiovascular disease (CVD) risk estimation has historically focused on outpatient data from whites according to age, sex, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), diabetes, smoking, and blood pressure (BP) information. Risk factors (RFs) and overall CVD risk are associated with genetic variations in genome-wide association studies (GWAS), and phenotypes have largely been based on single RF measurements using a Framingham approach. Previous research has focused on European Americans (EA), and generally has not included Veterans. Little information on CVD risk factor genes is available for African Americans (AA) or Hispanic Americans (HA), two population groups that are extremely important in the VA. The Million Veteran Program (MVP) cohort provides a unique opportunity to study genes and CVD risk among these subgroups, using MVP questionnaire data, electronic health record (EHR) information, and genetic data. We propose to address scientific gaps by focusing on multiple ethnicities, rare variants, and antecedent RF levels using the MVP cohort. In previous funding we created a virtual baseline exam for all MVP participants and we propose to further curate that information, extend research into new heart disease RFs and conditions, and use a longitudinal prospective study design. In addition to traditional CVD RFs such as lipids, smoking, diabetes, and BP that are already under investigation by our MVP research group, we propose to use GWAS to assess effects of genes on blood cell indices, inflammatory conditions, valvular heart disease, obstructive sleep apnea, and atrial fibrillation. Our research will assess gene-environment (diet quality, pharmacological treatment) effects, and will included assessment of current and antecedent RF levels. Methods will include diet quality adjustments using the Willett Food Frequency Questionnaire performed at the MVP baseline visit. Other methods will include pharmacologic treatment of CVD RFs to derive imputed untreated RF levels, and antecedent quantitative CVD RFs measured at VA outpatient visits up to 14 years before the MVP baseline visit when such data are available. We will perform common variant association studies (CVAS) and rare variant association studies (RVAS), testing for the association of genetic variants to quantitative CVD risk for incidence and period prevalence of a) coronary heart disease (CHD) [myocardial infarction (MI), coronary bypass grafting (CABG), percutaneous coronary intervention (PCI)] and b) atherothrombotic stroke, with comparison of effects by race and ethnicity, and c) recurrent events following an initial MI or stroke. Summary analyses will examine the multigenic association of CHD and stroke using the genetic risk score (GRS) of validated CVD-associated SNPs within and across ethnicity. This project will provide a platform for CVD incidence analyses for MVP participants across the VA in the future. The proposed study findings will allow for the comparison of the impact of genetic variants on heart disease RFs and atherosclerotic disease prevalence across AA, HA, and EA Veterans.

心血管疾病（CVD）风险估计在历史上一直集中在门诊数据上 白人根据年龄，性别，LDL-胆固醇（LDL-C），HDL-胆固醇（HDL-C），糖尿病，糖尿病， 吸烟和血压（BP）信息。风险因素（RF）和总体CVD风险是 与全基因组关联研究（GWAS）中的遗传变异相关， 表型主要基于使用Framingham的单RF测量 方法。以前的研究重点是欧洲人（EA），通常没有 包括退伍军人。关于CVD危险因素基因的信息很少可用于非洲 美国人（AA）或西班牙裔美国人（HA），两个人口群体极为 在VA中很重要。百万退伍军人计划（MVP）队列提供了一个独特的机会 使用MVP调查表数据，电子，研究这些亚组之间的基因和CVD风险 健康记录（EHR）信息和遗传数据。我们建议通过 专注于使用MVP队列的多种族裔，稀有变体和先前的RF水平。 在以前的资金中，我们为所有MVP参与者创建了虚拟基线考试，我们建议 为了进一步策划该信息，将研究扩展到新的心脏病RF和条件中， 并使用纵向前瞻性研究设计。除了传统的CVD RF，例如 我们的MVP研究已经在研究中，脂质，吸烟，糖尿病和BP已经在研究 小组，我们建议使用GWAS评估基因对血细胞指数的影响，炎症 条件，瓣膜心脏病，阻塞性睡眠呼吸暂停和心房颤动。我们的研究 将评估基因环境（饮食质量，药理治疗）效应，并将包括 评估当前和先例的RF水平。方法将包括饮食质量调整 使用在MVP基线访问中进行的Willett食品频率问卷。其他 方法将包括对CVD RF的药理处理以得出未经处理的RF 在VA门诊时测量的水平和先例定量CVD RF访问长达14年 在提供此类数据时，在MVP基线访问之前。我们将执行常见变体 协会研究（CVA）和稀有变体关联研究（RVA），测试 遗传变异与定量CVD风险的关联A） 冠心病（CHD）[心肌梗塞（MI），冠状动脉搭桥术（CABG）， 经皮冠状动脉干预（PCI）]和b）动脉瘤性中风，并进行比较 种族和种族的影响，以及c）初始MI或中风后的反复事件。概括 分析将使用遗传风险评分检查冠心病和中风的多基因关联 在种族中和跨种族中经过验证的CVD相关SNP的（GRS）。这个项目将提供 CVD发病率分析的平台将来对VA的MVP参与者进行了分析。这 拟议的研究发现将允许比较遗传变异对心脏的影响 AA，HA和EA退伍军人的疾病RFS和动脉粥样硬化疾病患病率。