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

• 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
• 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

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）：高血压影响近三分之一的成年人，是冠心病、中风和终末期肾病最常见的危险因素。它是占死亡总人数11%以上的主要或促成死亡的原因，2007年的医疗费用估计为664亿美元。血压在一生中稳步上升。因此，发现血压个体发生的分子因素可能是了解高血压的基础。拟议的研究代表了一项合作努力，利用现有标本、心血管疾病风险因素的高质量表型数据和最先进的分析方法，识别和复制影响纵向心血管疾病（CVD）风险因素概况的遗传效应，特别强调血压，并表征它们与相关环境因素的相互作用，特别是体重概况、身体健康、心理社会影响和饮食摄入。这些目标对于开发检测、治疗和预防高血压及其相关心血管疾病后果的新方法至关重要。主要背景是青年人冠状动脉风险发展（CARDIA），这是一项前瞻性、多中心调查，研究了5115名18-30岁的非裔美国人和白人在初始检查时的心血管疾病的自然史和病因。我们建议对1930名非裔美国人和2064名白人CARDIA参与者进行全基因组关联分析，以确定在从青年到中年早期的关键过渡时期，假设有15-20个基因与血压谱的个体间差异相关。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）的合作，将促进结果的复制。CARDIA队列提供了一个独特的机会，通过收集从青年到中年早期的生活方式、行为和生理风险因素的广泛数据，研究遗传变异对CVD风险因素的影响，这一时期CVD的发展和进展加速，但临床上很少发生公认的事件，最大限度地减少了与治疗这些事件相关的药物的混杂效应。或由于参与者心血管疾病相关死亡的潜在偏倚。