SNPs and Extent of Atherosclerosis (SEA) Study

SNP 和动脉粥样硬化程度 (SEA) 研究

基本信息

批准号：
7387349
负责人：
DAVID McLeod HERRINGTON
金额：
$ 176.04万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-15 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7387349
关键词：
Abdomen Accounting Admixture African American Ankle Area Arterial Fatty Streak Atherosclerosis Calcium Candidate Disease Gene Cardiovascular Diseases Case-Control Studies Caucasians Caucasoid Race Chinese People Chromosomes Clinical Cohort Studies Complex Coronary Coronary heart disease Coupled DNA DNA Resequencing Data Databases Development Disease Doctor of Medicine Documentation Early identification Ethnic group Evaluation Gene Frequency Genes Genetic Genome Genomics Genotype Haplotypes Hispanics Human Genome Individual Intervention Lead Location Measures Medial Numbers Outcome Pathway interactions Phenotype Research Design Research Personnel Resources Right coronary artery structure Risk Science Score Single Nucleotide Polymorphism Specimen Structure Sum Surface Technology Testing Therapeutic Intervention Thick Thoracic aorta Variant Youth base calcification cardiovascular risk factor case control cohort density design disorder risk gene environment interaction gene interaction genetic linkage analysis genetic variant genome wide association study indexing novel novel therapeutics prevent programs

项目摘要

DESCRIPTION (provided by applicant): The ongoing burden of cardiovascular disease emphasizes the need to develop new strategies to prevent and treat atherosclerosis. Several lines of evidence indicate that a significant portion of variability in risk for atherosclerosis is heritable. However, to date family-based linkage studies and candidate gene analyses have failed to discover genetic variants that account for most of this variation. Association studies are predicted to be more efficient than linkage studies to detect genetic variants that contribute to common complex phenotypes like atherosclerosis. However, in the past, adequate genome-wide association studies have been impractical due to limitations in genotyping capacity and incomplete documentation of the common variants in the human genome. Recently, these limitations have been overcome, making it possible to design association studies with excellent power to detect common variants contributing to disease risk. These technological developments, combined with the existence of several NHLBI sponsored cohorts with detailed phenotypic data on atherosclerosis provide a highly leveraged opportunity to search for genetic variants associated with early and extensive subclinical atherosclerosis. Discovering such variants could lead to new strategies for early identification of high risk subjects when aggressive intervention would be more likely to prevent the initial development of disease. In addition, identification of variants that predispose to atherosclerosis may suggest novel pathophysiologic pathways that could be explored as potential targets for new therapeutic interventions.

描述（由申请人提供）：心血管疾病的持续负担强调需要制定预防和治疗动脉粥样硬化的新策略。几条证据表明，动脉粥样硬化风险的大量变异性是可遗传的。但是，迄今为止，基于家庭的联系研究和候选基因分析未能发现造成大部分这种变异的遗传变异。预计关联研究比连锁研究更有效，可以检测遗传变异，从而有助于诸如动脉粥样硬化等常见的复杂表型。然而，由于基因分型能力的限制以及人类基因组中常见变异的局限性，全基因组的关联研究是不切实际的。最近，这些限制已经克服了，使设计具有良好能力的协会研究可以检测有助于疾病风险的共同变异。这些技术发展，结合了几个NHLBI赞助的队列，并具有有关动脉粥样硬化的详细表型数据，为寻找与早期且广泛的亚周期性动脉粥样硬化有关的遗传变异提供了高度杠杆化的机会。发现这种变体可能会导致新的策略，以便在积极的干预措施更有可能阻止初始疾病发展时，以早期识别高风险受试者。此外，鉴定易感动脉粥样硬化的变体可能表明可以将新的病理生理途径作为新的治疗干预措施的潜在靶标。