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）风险估计集中于根据年龄、性别、LDL-胆固醇（LDL-C）、HDL-胆固醇（HDL-C）、糖尿病、吸烟和血压（BP）信息的白人门诊数据。在全基因组关联研究（GWAS）中，风险因素（RF）和总体CVD风险与遗传变异相关，并且表型主要基于使用Fracket方法的单个RF测量。以前的研究主要集中在欧洲裔美国人（EA），通常不包括退伍军人。关于非洲裔美国人（AA）或西班牙裔美国人（HA）中CVD风险因子基因的信息很少，这两个人群在VA中非常重要。随着百万退伍军人计划（MVP）队列的可用性，我们有一个独特的机会来研究这些亚组中的基因和CVD风险。到目前为止，还没有开发出将MVP问卷和遗传数据与退伍军人的电子医疗保健信息联系起来的方法。我们建议使用MVP队列，通过关注多种族、罕见变异和先前的风险因素水平来解决科学差距。在拟议的研究中，我们首先创建一个虚拟的基线检查，通过开发方法，使用系统的方法将MVP基线检查的数据链接到VA电子健康记录。退伍军人的结果受美国地理区域的影响，种族/民族、门诊就诊频率和其他变量。基于我们处理MVP问卷数据和电子医疗保健数据的系统方法，我们评估了常见和罕见等位基因与CVD RF在因果途径中的全基因组关联，并考虑了环境（饮食质量，药物治疗）以及当前和既往RF水平的评估。方法包括在MVP基线访视时使用Willett食物频率问卷进行的单次VA门诊定量CVD RF（LDL-C、非HDL-C、甘油三酯、体重指数）测量，伴和不伴饮食质量调整。其他方法包括CVD RF的药物治疗，以推导插补的未治疗RF水平，以及在MVP基线访视前5年和10年VA门诊访视时测量的既往定量CVD RF（如果此类数据可用）。我们将进行常见变异相关性研究（CVAS）和罕见变异相关性研究（RVAS），检测遗传变异与a）流行性冠心病（CHD）[心肌梗死、冠状动脉旁路移植术（CABG）史、经皮冠状动脉介入治疗（PCI）史]和B）流行性动脉粥样硬化血栓形成性卒中的定量CVD风险的相关性，并比较人种和种族的影响，和c）使用种族内和种族间经验证的CVD相关SNP的遗传风险评分（GRS）检查CHD和中风的多基因关联。该项目将为未来VA的MVP参与者提供CVD发病率分析平台。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风险因素和动脉粥样硬化疾病患病率的影响。CVD占退伍军人的一个非常大的医疗保健负担。该项目将调查不同种族和种族的MVP参与者中CVD风险因素的遗传和环境决定因素的作用。