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

心血管疾病(CVD)风险评估历来侧重于 按年龄、性别、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、糖尿病、 吸烟和血压(BP)信息。风险因素(RF)和总体心血管疾病风险为 与全基因组关联研究中的遗传变异有关，以及 表型在很大程度上是基于使用Framingham的单个RF测量 接近。以前的研究集中在欧洲裔美国人(EA)上，通常没有 包括退伍军人。非洲关于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 在退伍军人事务部很重要。百万退伍军人计划(MVP)队列提供了一个独特的机会 为了研究这些亚组中的基因和心血管疾病风险，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，专注于多种族、罕见变异和先前的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准考试，我们建议 为了进一步精选这些信息，扩大对新的心脏病RFS和疾病的研究， 并采用纵向前瞻性研究设计。除了传统的CVD RFS之外，例如 血脂、吸烟、糖尿病和BP已经在我们的MVP研究中进行了调查 小组，我们建议使用GWAS来评估基因对血细胞指标、炎症的影响 病症、心脏瓣膜病、阻塞性睡眠呼吸暂停和房颤。我们的研究 将评估基因-环境(饮食质量、药物治疗)的影响，并将包括 评估当前和以前的射频水平。方法将包括调整饮食质量 使用在MVP基线访问时执行的Willett食物频率调查问卷。其他 方法将包括对CVD RF进行药物治疗，以获得归因于未经治疗的RF 水平，以及在退伍军人管理局门诊就诊前测量的定量心血管RFS，最长可达14年 在MVP基线访问之前，当这些数据可用时。我们将执行常见的变体 关联研究(CVA)和罕见变异关联研究(RVA)，测试 遗传变异与定量心血管疾病风险之间的关系 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)动脉粥样硬化血栓形成卒中，与 种族和民族的影响，以及c)首次心肌梗死或中风后的复发事件。摘要 分析将使用遗传风险分数来检查冠心病和中风的多基因关联。 种族内和种族间有效的与心血管疾病相关的SNPs(GR)。该项目将提供 未来为退伍军人管理局的MVP参与者提供心血管事件分析的平台。这个 拟议的研究结果将允许比较基因变异对心脏的影响 疾病RF和动脉粥样硬化性疾病在AA、HA和EA退伍军人中的患病率。

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.