GWAS of longitudinal blood pressure profiles from young adulthood to middle-age

从青年期到中年纵向血压曲线的 GWAS

基本信息

批准号：
7514759
负责人：
MYRIAM FORNAGE
金额：
$ 57.58万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-20 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7514759
关键词：
Accounting Adult Affect African American Age Algorithms Arts Atherosclerosis Behavior Blood Pressure Body Composition Body Weight Candidate Disease Gene Cardiovascular Diseases Cardiovascular system Cause of Death Cessation of life Cohort Studies Collaborations Communities Coronary artery Coronary heart disease DNA Data Data Analyses Detection Development Dietary Sodium Dietary intake Doctor of Philosophy End stage renal failure Environment Environmental Risk Factor Etiology Event Family Fatty acid glycerol esters Framingham Heart Study Functional disorder Genes Genetic Genetic Variation Genome Genotype Goals Growth Haplotypes Health Health Care Costs Heart High Blood Pressure Hypertension Individual Intake Investigation Life Life Style Linkage Disequilibrium Literature Measures Molecular Morbidity - disease rate Natural History Numbers Participant Pharmaceutical Preparations Phenotype Physical Fitness Physiological Prevention Preventive Psychosocial Factor Publishing Research Research Personnel Resources Risk Risk Factors Scientist Single Nucleotide Polymorphism Social Aspects of Cancer Specimen Staging Stroke Structure Therapeutic Time Variant analytical method base cardiovascular disorder risk caucasian American cohort design gene discovery genome wide association study middle age mortality novel strategies programs prospective young adult

项目摘要

DESCRIPTION (provided by applicant): High blood pressure, or hypertension, affects nearly one in three adults and is the most common risk factor for coronary heart disease, stroke, and end-stage renal disease. It is a primary or contributing cause of death in over 11 % of the total number of deaths, and accounted for an estimated $66.4 billion in healthcare costs in 2007. Blood pressure rises steadily throughout life. Therefore, discovering the molecular factors that underlie blood pressure ontogeny may be fundamental to understanding hypertension. The proposed research represents a collaborative effort to use existing specimens, high-quality phenotypic data on cardiovascular disease risk factors, and state-of-the-art analytical methods to identify and replicate genetic effects influencing longitudinal cardiovascular disease (CVD) risk factors profiles, with a special emphasis on blood pressure, and to characterize their interactions with relevant environmental factors, specifically body weight profiles, physical fitness, psychosocial influences, and dietary intake. These goals are fundamental to developing new approaches to detection, treatment, and prevention of high blood pressure and its associated CVD consequences. The primary setting is that of the Coronary Artery Risk Development in Young Adults (CARDIA), a prospective, multi-center investigation of the natural history and etiology of cardiovascular disease in 5,115 African-Americans and Whites 18-30 years old at the time of initial examination. We propose to conduct whole genome association analyses on 1,930 African-American and 2,064 white CARDIA participants with available DNA to identify an assumed 15-20 genes associated with inter-individual variation in blood pressure profiles during the critical transition period from young adulthood to early middle-age. Replication of results will be facilitated through collaborations with the Atherosclerosis Risk In Communities (ARIC) study, the Rochester Family Heart Study (RFHS), and the Bogalusa Heart Study (BHS). The CARDIA cohort provides a unique opportunity to examine the context-dependent effects of genetic variation influencing CVD risk factors profiles, by virtue of the extensive data on lifestyle, behavior, and physiologic risk factors collected from young adulthood to early middle-age, a period when the development and progression of CVD accelerates, but when few clinically recognized events have occurred, minimizing confounding effects of drugs associated with treatment of such events, or potential bias due to CVD-related death of the participants.

描述（由申请人提供）：高血压或高血压会影响近三分之一的成年人，是冠心病，中风和终末期肾脏疾病的最常见危险因素。它是死亡总数的11％以上的主要或造成死亡原因，2007年估计为664亿美元的医疗保健费用。血压在一生中稳步上升。因此，发现血压本体发育基础的分子因素可能是理解高血压的基础。拟议的研究代表了一种协作努力，以使用现有标本，高质量的表型数据对心血管疾病的危险因素以及最新的分析方法，以识别和复制遗传效应，从而影响纵向心血管疾病（CVD）的遗传效应（CVD），并特别强调其互动性，并具有特定的身体互动性，并具有相关性的互动性，并具有相关性，并具有相关性，并且具有相关性，并具有相关性，并且具有相关性的互动性，并且具有相关性的互动性。影响和饮食摄入量。这些目标是开发新的检测，治疗和预防高血压及其相关CVD后果的基础。主要的环境是年轻人（CADCIA）的冠状动脉风险发展，这是对初次检查时5,115名非裔美国人和白人的预期，对心血管疾病的自然病史和病因的前瞻性，多中心的研究。我们建议对1,930名非裔美国人和2,064名具有可用DNA的白人Cardia参与者进行整个基因组关联分析，以识别从年轻成年期到早期中期的关键过渡期间与血压差异相关的15-20个基因。通过与社区动脉粥样硬化风险（ARIC）研究，罗切斯特家庭心脏研究（RFHS）和Bogalusa心脏研究（BHS）合作，将促进结果的复制。 Cardia队列提供了一个独特的机会，可以检查影响CVD风险因素的遗传变异的上下文效果，这是由于有关生活方式，行为，行为和生理风险因素的广泛数据，从成年期到中年早期收集到早期的生理危险因素，这是CVD的发展和临床上发生的事件，而发生了临床上的事件，而发生了临床范围的造成的，而发生了临床范围的造成的影响，而造成了临床上的影响，而发生了临床上的事件，则发生了造成的事件，而发生了造成的事件，而发生了造成的事件，则发生了造成的事件。由于参与者与CVD相关的死亡而导致的偏见。