Cardiovascular Disease Risk Factors, Prevalent Cardiovascular Disease, 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、流行的心血管疾病和遗传学

• 批准号: 9031899
• 负责人: Kelly Cho
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-10-01 至 2018-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9031899
• 关键词: Address; Affect; African American; Age; Ambulatory Care; Ambulatory Care Facilities; American; Atherosclerosis; Blood Pressure; Body mass index; Cardiovascular Diseases; Clinic Visits; Clinical; Cohort Studies; Computerized Patient Records; Coronary Artery Bypass; Coronary heart disease; Data; Data Linkages; Databases; Development; Diabetes Mellitus; Diet; Disease Outcome; Electronic Health Record; Environment; Ethnic Origin; Ethnic group; European; Event; Food; Fostering; Frequencies; Future; Genes; Genetic; Genetic Determinism; Genetic Risk; Genetic Variation; Geographic Locations; Healthcare; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Hispanic Americans; Hospitalization; Incidence; Intervention; LDL Cholesterol Lipoproteins; Link; Measurement; Measures; Medical Records; Medical center; Methods; Myocardial Infarction; Outcome; Outpatients; Participant; Pathway interactions; Patient Self-Report; Persons; Pharmacological Treatment; Phenotype; Population; Population Group; Prevalence; Primary Health Care; Process; Questionnaires; Race; Recording of previous events; Reporting; Research; Risk Estimate; Risk Factors; Role; Single Nucleotide Polymorphism; Smoking; Stroke; Subgroup; System; Testing; Time; Triglycerides; United States Centers for Medicare and Medicaid Services; Variant; Vascular Diseases; Veterans; Visit; base; blood lipid; cardiometabolic risk; cardiovascular disorder risk; care burden; clinical risk; cohort; collaborative environment; disorder risk; experience; genetic association; genetic variant; genome wide association study; percutaneous coronary intervention; programs; public health relevance; rare variant; sex; virtual

 DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) risk estimation has 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. There is little information on CVD risk factor genes in African Americans (AA) or Hispanic Americans (HA), two population groups that are extremely important in the VA. With the availability of the Million Veteran Program (MVP) cohort, we have a unique opportunity to study genes and CVD risk among these subgroups. Up to now methods have not been developed to link MVP questionnaire and genetic data to the Veteran's electronic healthcare information. We propose to address scientific gaps by focusing on multiple ethnicities, rare variants, and antecedent risk factor levels using the MVP cohort. In the proposed study, we first create a virtual baseline exam by developing methods to link data from MVP baseline examination to the VA electronic health record using a systematic approach. Results for Veterans are influenced by geographic region in the U.S., race/ethnicity, frequency of outpatient clinic visits, and other variables. Based on our systematic approach of handling MVP questionnaire data and the electronic healthcare data, we assess the genome-wide associations of both common and rare alleles with CVD RFs in causal pathways, with consideration of the environment (diet quality, pharmacological treatment), and assessment of current and antecedent RF levels. Methods include single VA outpatient measurements of quantitative CVD RFs (LDL-C, non- HDL-C, triglycerides, body mass index) with and without diet quality adjustment using the Willett Food Frequency Questionnaire performed at the MVP baseline visit. Other methods include pharmacologic treatment of CVD RFs to derive imputed untreated RF levels, and antecedent quantitative CVD RFs measured at VA outpatient visits 5 and 10 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 the association of genetic variants to quantitative CVD risk for a) prevalent coronary heart disease (CHD) [myocardial infarction, history of coronary bypass grafting (CABG), history of percutaneous coronary intervention (PCI)] and b) prevalent atherothrombotic stroke, with comparison of effects by race and ethnicity, and c) 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. Furthermore, the proposed study findings will allow for the comparison of the impact of genetic variants on cardio metabolic RFs risk factors and atherosclerotic disease prevalence across AA, HA, and EA Veterans. CVD accounts for an extremely large health care burden in veterans. This project will investigate the role of genetic and environmental determinants of CVD risk factors in MVP participants across different ethnic and racial groups.

 描述（由申请人提供）： 心血管疾病 (CVD) 风险评估重点关注白人的门诊数据，根据年龄、性别、低密度脂蛋白胆固醇 (LDL-C)、高密度脂蛋白胆固醇 (HDL-C)、糖尿病、吸烟和血压 (BP) 信息。风险因素 (RF) 和整体 CVD 风险与全基因组关联研究 (GWAS) 中的遗传变异相关，表型很大程度上基于使用弗雷明汉方法的单一 RF 测量，之前的研究主要针对欧洲裔美国人。 (EA)，并且通常不包括退伍军人，关于非裔美国人 (AA) 或西班牙裔美国人 (HA) 的 CVD 危险因素基因的信息很少，这两个群体在 VA 中极为重要。退伍军人计划 (MVP) 队列，我们​​有一个独特的机会来研究这些亚组的基因和 CVD 风险，到目前为止，尚未开发出将 MVP 调查问卷和遗传数据与退伍军人电子医疗信息联系起来的方法。通过关注多个种族、罕见变体，在拟议的研究中，我们首先通过开发方法，使用系统方法将 MVP 基线检查的数据与 VA 电子健康记录联系起来，创建虚拟基线检查。根据我们处理 MVP 问卷数据和电子医疗数据的系统方法，我们评估了常见和罕见等位基因与 CVD 的全基因组关联。因果关系中的 RF方法包括对 CVD RF 进行单次 VA 门诊测量（LDL-C、非 HDL-C、甘油三酯、体重指数）。 ）使用在 MVP 基线访视时进行的 Willett 食物频率问卷进行或不进行饮食质量调整其他方法包括对 CVD RF 进行药物治疗，以得出估算的未治疗 RF 水平和前因。当获得 MVP 基线访视前 5 年和 10 年定量数据时，在 VA 门诊就诊时测量的 CVD RF 将进行常见变异关联研究 (CVAS) 和罕见变异关联研究 (RVAS)，测试遗传变异与定量 CVD 风险的关联。 a) 流行的冠心病 (CHD) [心肌梗塞、冠状动脉旁路移植术 (CABG) 病史、经皮冠状动脉介入治疗 (PCI) 病史] 和 b) 流行的动脉粥样硬化血栓性卒中，并进行效果比较c) 使用种族内和跨种族的经验证的 CVD 相关 SNP 的遗传风险评分 (GRS) 检查 CHD 和中风的多基因关联。该项目将为跨种族的 MVP 参与者提供一个进行 CVD 发病率分析的平台。此外，拟议的研究结果将允许比较遗传变异对 AA、HA 和 EA 退伍军人的心脏代谢 RF 危险因素和动脉粥样硬化疾病患病率的影响。该项目将调查不同民族和种族群体的 MVP 参与者中 CVD 风险因素的遗传和环境决定因素的作用。