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: 7689903
• 负责人: MYRIAM FORNAGE
• 金额: $ 55.94万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7689903
• 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; Hypertension; Individual; Intake; Investigation; Life; Life Style; Linkage Disequilibrium; Literature; Measures; Molecular; Morbidity - disease rate; Natural History; Participant; Pharmaceutical Preparations; Phenotype; Physical Fitness; Physiological; Prevention; Preventive; Psychosocial Factor; Psychosocial Influences; Publishing; Research; Research Personnel; Resources; Risk; Risk Factors; Scientist; Single Nucleotide Polymorphism; Specimen; Staging; Stroke; Structure; Therapeutic; Time; Variant; analytical method; base; cardiovascular disorder risk; caucasian American; cohort; data sharing; 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(申请人提供)：高血压，或高血压，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。它是死亡总人数的11%以上的主要或促成死亡的原因，估计在2007年的医疗费用中占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。这项拟议的研究代表了一项合作努力，利用现有的样本、关于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来识别和复制影响纵向心血管疾病(CVD)风险因素谱的遗传效应，并特别强调血压，并表征它们与相关环境因素的相互作用，特别是体重谱、身体健康、心理社会影响和饮食摄入量。这些目标是开发检测、治疗和预防高血压及其相关心血管后果的新方法的基础。主要背景是青年冠状动脉风险发展(CARDIA)，这是一项前瞻性的多中心调查，对初次检查时年龄在18-30岁的5115名非裔美国人和白人的心血管疾病的自然历史和病因进行调查。我们建议对1,930名非洲裔美国人和2,064名拥有可用DNA的CARDIA白人参与者进行全基因组关联分析，以确定在从年轻成年到中年早期的关键过渡时期，与血压谱个体间差异相关的假定15-20个基因。通过与社区动脉粥样硬化风险研究(ARIC)、罗切斯特家庭心脏研究(RFHS)和博加卢萨心脏研究(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，通过从年轻成人到中年早期收集的关于生活方式、行为和生理风险因素的广泛数据，检查影响心血管疾病风险因素谱的遗传变异的上下文相关效应，这段时期心血管疾病的发展和进展加速，但很少发生临床公认的事件，将与此类事件的治疗相关的药物的混淆效应降至最低，或参与者因心血管疾病相关死亡而产生的潜在偏差。

项目成果

Genome-wide association study of L-arginine and dimethylarginines reveals novel metabolic pathway for symmetric dimethylarginine.

• DOI: 10.1161/circgenetics.113.000264
• 发表时间: 2014-12
• 期刊: Circulation. Cardiovascular genetics
• 作者: Lüneburg N;Lieb W;Zeller T;Chen MH;Maas R;Carter AM;Xanthakis V;Glazer NL;Schwedhelm E;Seshadri S;Ikram MA;Longstreth WT Jr;Fornage M;König IR;Loley C;Ojeda FM;Schillert A;Wang TJ;Sticht H;Kittel A;König J;Benjamin EJ;Sullivan LM;Bernges I;Anderssohn M;Ziegler A;Gieger C;Illig T;Meisinger C;Wichmann HE;Wild PS;Schunkert H;Psaty BM;Wiggins KL;Heckbert SR;Smith N;Lackner K;Lunetta KL;Blankenberg S;Erdmann J;Munzel T;Grant PJ;Vasan RS;Böger RH
• 通讯作者: Böger RH