Genetic Mechanisms of Arteriosclerosis in Hypertensive Sibships

高血压同胞动脉硬化的遗传机制

• 批准号: 8758883
• 负责人: Sharon L Kardia
• 金额: $ 70.05万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8758883
• 关键词: African American; Ankle; Arterial Disorder; Arteries; Arterioloscleroses; Arteriosclerosis; Atherosclerosis; Biological; Blood Pressure; Brain; Cardiac; Cerebrum; Chronic Kidney Failure; Clinical; Communities; DNA Sequence; Data; Dementia; Disease; Epidemiology; Exons; Family; Gene Expression; Gene Mutation; Generations; Genes; Genetic; Genetic Risk; Genetic Variation; Genome; Genomics; Health Care Costs; Heart; Heart failure; Hypertension; Individual; Ischemic Brain Injury; Kidney; Kidney Diseases; Leg; Measures; Methods; Myocardial Infarction; Not Hispanic or Latino; Organ; Outcome; Participant; Peripheral; Population; Population Attributable Risks; Predisposition; Risk; Risk Factors; Sampling; Stroke; Time; United States; Variant; base; body system; claudication; cohort; coronary artery calcification; cost effective; design; exome; familial hypertension; genetic epidemiology; genetic variant; high risk; indexing; public health relevance; rare variant; risk variant; transcriptomics

DESCRIPTION (provided by applicant): The Genetic Epidemiology Network of Arteriopathy (GENOA) was initiated in 1995 to study the genetics of hypertension and its arteriosclerotic complications in sibships. Arteriosclerosis (i.e., atherosclerosis and arteriolosclerosis) of the cardiac, cerebral, renal, and peripheral arteries leads to target organ damage and clinical sequelae such as heart attack, heart failure, stroke, dementia, chronic kidney disease, and claudication. In this application, we propose to conduct an exome-wide association study (Aim 1) and transcriptomic profiling (Aim 2) as cost-effective methods of identifying and studying functional variations in the 1020 GENOA African-American and non-Hispanic White sibships (N=2912) who are at high risk of developing a wide range of arteriosclerotic clinical outcomes. The GENOA cohort provides a unique opportunity to assess the phenotypic impact of rare variants that naturally replicate within a sibship, but may not be seen again even in large epidemiological populations. The GENOA community-based sampling of hypertensive sibships was explicitly designed to study the genetics of multiple late-onset arteriosclerotic diseases that typically become clinically apparent only in the upper generations of families. In order to ultimately identify "at risk" individuals and estimate the cumulative burden of genetic risk allele in two U.S. populations (Aim 3) we will estimate genetic risk scores and assess the attributable fraction of phenotypic variation explained by these new genetic variations.

描述（由申请人提供）：1995年启动了动脉疾病的遗传流行病学网络（GENOA），研究了高血压及其动脉硬化并发症的遗传学。心脏，大脑，肾脏和周围动脉的动脉粥样硬化（即动脉粥样硬化和动脉粥样硬化）会导致靶心器官损伤和临床后遗症，例如心脏病，心力衰竭，中风，痴呆，痴呆，慢性肾脏疾病和claudication。 In this application, we propose to conduct an exome-wide association study (Aim 1) and transcriptomic profiling (Aim 2) as cost-effective methods of identifying and studying functional variations in the 1020 GENOA African-American and non-Hispanic White sibships (N=2912) who are at high risk of developing a wide range of arteriosclerotic clinical outcomes.热那亚队列提供了一个独特的机会，可以评估自然复制的稀有变体的表型影响，但即使在大量的流行病学人群中也可能不会再次看到。高血压sibship的基于热那亚社区的采样旨在研究多种晚期动脉硬膜菌疾病的遗传学 通常仅在家庭的上几代就变得明显。为了最终确定“处于风险”的个体，并估计了两个美国人群中遗传风险等位基因的累积负担（AIM 3），我们将估算遗传风险评分，并评估由这些新遗传变异所解释的表型变异的可归因部分。