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: 10516091
• 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 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10516091
• 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; Classification; Cohort Studies; Complete Blood Count; Coronary Artery Bypass; Coronary heart disease; Data; Data Element; Data Sources; Databases; Development; Diabetes Mellitus; Diet; Disease; 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; Hispanic Americans; Incidence; Inflammatory; Inflammatory Arthritis; Intake; Investigation; LDL Cholesterol Lipoproteins; Link; Lipids; 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 Care; Process; Questionnaires; Race; Recording of previous events; Recurrence; Research; Research Design; Risk; Risk Estimate; Risk Factors; Role; Smoking; Stroke; Subgroup; Techniques; Testing; Time; Triglycerides; Variant; Vascular Diseases; Veterans; Visit; White Blood Cell Count procedure; Work; adjudication; blood glucose regulation; cardiovascular disorder risk; cardiovascular effects; cardiovascular risk factor; clinical diagnosis; clinical risk; cohort; genetic risk factor; genetic variant; genome wide association study; healthy aging; heart disease risk; indexing; longitudinal, prospective study; 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; 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）风险估计历来侧重于门诊数据， 根据年龄、性别、LDL-胆固醇（LDL-C）、HDL-胆固醇（HDL-C）、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，以及 表型在很大程度上是基于单RF测量使用Fragrance approach.以前的研究集中在欧洲美国人（EA），一般没有 包括退伍军人。关于非洲人心血管疾病危险因素基因的信息很少 美国人（AA）或西班牙裔美国人（HA），这两个人口群体是非常 重要的是在VA。百万退伍军人计划（MVP）队列提供了一个独特的机会 研究基因和心血管疾病的风险在这些亚组中，使用MVP问卷数据，电子 健康记录（EHR）信息和遗传数据。我们建议通过以下方式解决科学差距 使用MVP队列，重点关注多种族、罕见变异和既往RF水平。 在之前的资助中，我们为所有MVP参与者创建了一个虚拟基线考试， 为了进一步收集这些信息，将研究扩展到新的心脏病RF和病症， 并采用纵向前瞻性研究设计。除了传统的CVD RF之外， 血脂、吸烟、糖尿病和血压已经在我们的MVP研究中进行了调查 组，我们建议使用GWAS评估基因对血细胞指数，炎症， 心脏病、心脏瓣膜病、阻塞性睡眠呼吸暂停和心房纤颤。我们的研究 将评估基因-环境（饮食质量、药物治疗）效应，并将包括 评估当前和先前的RF水平。方法将包括饮食质量的调整 使用MVP基线访视时进行的Willett食物频率问卷。其他 方法将包括CVD RF的药物治疗，以推导插补的未治疗RF 水平以及VA门诊就诊时测量的先前定量CVD RF（长达14年） 在MVP基线访视之前，如果此类数据可用。我们将执行普通变量 相关性研究（CVAS）和罕见变异相关性研究（RVAS）， a）遗传变异与CVD发病率和时期患病率的定量风险的关联 冠心病（CHD）[心肌梗死（MI），冠状动脉旁路移植术（CABG）， 经皮冠状动脉介入治疗（PCI）]和B）动脉粥样硬化性卒中，比较 人种和种族的影响，以及c）初始MI或卒中后的复发事件。总结 分析将使用遗传风险评分检查CHD和卒中的多基因关联 (GRS)在种族内和种族间验证的CVD相关SNP。本项目将提供 一个平台，用于未来VA MVP参与者的CVD发病率分析。的 拟议的研究结果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RF和动脉粥样硬化疾病患病率。