Genotypes, Haplotypes, and Blood Pressure Change from Childhood to Adulthood

从童年到成年的基因型、单倍型和血压变化

• 批准号: 7932874
• 负责人: DAVID MICHAEL HALLMAN
• 金额: $ 25.5万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932874
• 关键词: 14 year old; 18 year old; Adolescence; Adolescent; Adult; Affect; African American; Age; Age-Years; Alleles; Blood Pressure; Candidate Disease Gene; Child; Childhood; Chromosomes; Cohort Studies; Communities; Complement; Consent; DNA; Data; Development; Enrollment; Gene Mutation; Genes; Genetic; Genetic Variation; Genotype; Haplotypes; Heart; Human; Hypertension; Individual; Knowledge; Lipids; Longevity; Measurement; Measures; Methods; Mutation; Obesity; Pathology; Pattern; Phenotype; Play; Population; Preventive; Research; Resources; Risk; Risk Factors; Role; Sampling; Serum; Single Nucleotide Polymorphism; Study Subject; Testing; Texas; Time; United States; Variant; age related; base; blood pressure regulation; cardiovascular disorder risk; cohort; critical period; follow-up; genetic analysis; medical examination; public health relevance; trait

DESCRIPTION (provided by applicant): Hypertension affects nearly one-third of adults over age 20 in the United States. While hypertension is found in <10% in adults 20 - 34 years of age, it develops over a period of years, and blood pressure levels in children and adolescents are correlated with levels in adults. It is clear that genes play a significant role in regulating blood pressure, but little is known about the effects of genetic variation on the blood pressure changes that occur with age. Identifying the genes and mutations that affect blood pressure change from childhood, through adolescence, and into adulthood is necessary if are to understand the pathology of hypertension and target preventive measures most effectively. The Bogalusa Heart Study (BHS), which began as a study of cardiovascular disease (CVD) risk factors in children but evolved to cover the development of CVD risk factors from childhood into adulthood, offers a matchless resource for investigating the genetic factors influencing within-individual changes over time from childhood to adulthood in blood pressure and other CVD risk factors. We propose to investigate 3072 single-nucleotide polymorphisms (SNPs), both individually and as multilocus haplotypes (combinations of SNP alleles on a single chromosome), in 115 genes known or strongly suspected to affect blood pressure and risk of hypertension, using 1735 BHS subjects who consented to participate in studies of the genetics of CVD risk factors. Of these, 1687 (97.2%) were examined at least twice. The sample includes 1195 whites (with 5927 examinations) and 540 African Americans (with 2677 examinations); subjects were from 3 - 38 years of age when examined. Multilevel regression will be used to measure the effect of individual SNPs on longitudinal blood pressure profiles and identify those that affect age-related changes in blood pressure. In genes in which individual SNPs show significant associations, follow-up multilocus analyses will use evolutionary relationships among haplotypes to determine appropriate sets of haplotype comparisons to identify specific haplotypes associated with blood pressure changes over time and aid in locating functional mutations while reducing the number of necessary tests and increasing statistical power. All SNPs and haplotypes showing positive associations in the BHS cohort will be genotyped and analyzed in a replication sample of 506 whites (with 4503 examinations) and 136 African Americans (with 1007 examinations) drawn from Project HeartBeat!, a study of CVD risk factors in which schoolchildren from two Texas communities were enrolled at 8, 11, or 14 years of age, then received medical examinations 3 times a year for 4 years. The proposed research, involving the only two cohorts for whom extensive longitudinal data exist for biracial populations that include substantial numbers of African Americans, will greatly extend our knowledge of the genetic factors that affect blood pressure over a large portion of the human lifespan. Because many genes that affect blood pressure may also affect traits such as obesity and serum lipid levels, the proposed research will also provide opportunities to investigate genes affecting changes in other CVD risk factors. PUBLIC HEALTH RELEVANCE: Hypertension affects nearly one-third of adults in the United States, and though frank hypertension is uncommon in adults under 34 years of age, blood pressure levels in children and adolescents are correlated with levels in adults. It is clear that genes play a significant role in regulating blood pressure, but little is known about the effects of genes on the blood pressure changes that occur with age. Our proposed study will investigate genes likely to affect blood pressure changes over time in individuals 3-38 years of age, and will greatly extend our knowledge of the genetic factors that affect blood pressure over a large portion of the human lifespan.

描述（由申请人提供）：高血压影响美国20岁以上的成年人中有近三分之一。虽然在成年人20至34岁的成年人中发现高血压<10％，但它在多年内发展，儿童和青少年的血压水平与成年人的水平相关。显然，基因在调节血压中起着重要作用，但是对遗传变异对年龄发生的血压变化的影响知之甚少。如果要最有效地了解高血压和靶向预防措施的病理，则必须识别影响血压变化的基因和突变，直到青春期到成年是必要的。 Bogalusa心脏研究（BHS）最初是对儿童心血管疾病（CVD）危险因素的研究，但旨在涵盖从儿童期到成年的CVD危险因素的发展，为研究遗传因素提供了无与伦比的资源，用于研究影响从儿童到血液际血压和其他CVD风险和其他CVD危险中的个人内部变化的遗传因素。我们建议研究3072个单独和作为多焦点单倍型（单个染色体上SNP等位基因的组合）的3072个单核苷酸多态性（SNP），在115个基因或强烈怀疑会影响血压和使用1735 BHS受试者的血压和风险的风险中，这些受试者同意了危险因素，该研究是在研究中，该研究的危险因素是在研究中的研究。其中，至少两次检查了1687年（97.2％）。该样本包括1195名白人（有5927次检查）和540名非裔美国人（2677次检查）；受试者在检查时从3-38岁开始。多级回归将用于衡量单个SNP对纵向血压谱的影响，并确定那些影响与年龄相关的血压变化的影响。在单个SNP显示显着关联的基因中，随访多头骨分析将使用单倍型之间的进化关系来确定适当的单倍型比较集，以识别与随时间变化相关的特定单倍型，并有助于定位功能突变，同时减少必要的测试数量和增加统计功率。所有在BHS队列中显示积极关联的SNP和单倍型将在506个白人（有4503次检查）和136名非裔美国人（有1007次检查）中进行基因分型和分析，并从Project Heartbeat中得出14次的cvd危险因素，并在两位年龄段的CVD危险因素中进行了研究，该研究是在两个年龄段的CVD危险因素中进行的。一年4年的时间。拟议的研究涉及唯一的两个人群，其中包括大量非洲裔美国人的混血儿人群存在广泛的纵向数据，这将大大扩展我们对影响血压在大部分人类寿命上影响血压的遗传因素的了解。由于许多影响血压的基因也可能影响肥胖和血清脂质水平等特征，因此拟议的研究还将提供研究影响其他CVD风险因素变化的基因。 公共卫生相关性：高血压影响美国近三分之一的成年人，尽管弗兰克高血压在34岁以下的成年人中并不常见，但儿童和青少年的血压水平与成年人的水平相关。显然，基因在调节血压中起着重要作用，但是对基因对随着年龄的增长发生的血压变化的影响知之甚少。我们提出的研究将研究3-38岁个个体随时间变化的基因，并将大大扩展我们对影响血压在人类寿命的很大一部分的遗传因素的了解。