Genes, Hormomes, Growth, and Body Fat: Project HeartBeat

基因、激素、生长和体脂：心跳计划

• 批准号: 7320966
• 负责人: DAVID MICHAEL HALLMAN
• 金额: $ 25.67万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-06 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7320966
• 关键词: Abdomen; Accounting; Adipose tissue; Adolescence; Adolescent; Adult; Adverse effects; Affect; African American; Age; Age-Years; Algorithms; Alleles; Biological; Body Composition; Body Size; Body fat; Body mass index; Body measure procedure; Candidate Disease Gene; Cardiovascular Diseases; Childhood; Communities; DNA; Data; Databases; Deposition; Development; Diet; Endocrine system; Enrollment; Environment; Environmental Risk Factor; Exercise; Facility Construction Funding Category; Fatty acid glycerol esters; Female; Gene Targeting; Genes; Genetic; Genetic Polymorphism; Genotype; Growth; Growth and Development function; Haplotypes; Health; High Prevalence; Hormonal Change; Individual; Knowledge; Length; Longitudinal Studies; Measures; Modeling; Mutation; Not Hispanic or Latino; Obesity; Participant; Pathway interactions; Pattern; Peripheral; Phenotype; Prevalence; Principal Investigator; Promoter Regions; Puberty; Public Health; Range; Risk Factors; Sampling; Single Nucleotide Polymorphism; Staging; Texas; Time; Triceps Brachii Muscle; Variant; cardiovascular disorder risk; cardiovascular risk factor; cohort; critical developmental period; genetic variant; genome wide association study; programs; trait; waist circumference

DESCRIPTION (provided by applicant): Obesity is increasingly recognized as a major public health problem that is showing an alarming rise in prevalence in young people. While environmental factors, such as high-fat diets and lack of exercise, account for much of this rise, genetic differences may make some people more prone to obesity than others, even when diet and activity levels are similar among them. Obesity often has its genesis during childhood and, especially, adolescence, when differences among individuals in body fat amount and distribution tend to develop during puberty. It is thus important to understand the factors that affect growth, development, and body composition during this period. We will investigate the genetic factors that influence growth and body fat deposition during adolescence by using data and biological samples previously collected during Project HeartBeat!, a longitudinal study of cardiovascular disease risk factor development during childhood and adolescence. In two Texas communities, schoolchildren from 8-18 years of age were measured up to 3 times annually over a 4-year period, encompassing the ages when puberty normally occurs and adult body habitus usually develops. Subjects were enrolled at 8, 11, or 14 years of age to establish 3 separate cohorts that would overlap in age as the study progressed and permit construction of a synthetic cohort encompassing the full 10-year age range of the participants. The sample included 136 African Americans (70 females) and 506 non-Hispanic whites (250 females), with a mean of 8.6 examinations per subject. In each individual, we will genotype multiple single-nucleotide polymorphisms (SNPs) in 80 genes from hormonal systems important in growth and development, emphasizing genes known or suspected to affect body size and body fat distribution. In each gene, all promoter region and exonic SNPs, together with haplotype-tagging SNPs identified in public databases by 3 different algorithms, will be typed. A 3-stage algorithm will be used to identify a subset of SNPs in which multilevel mixed models will be used to analyze the associations of both individual variants and multilocus haplotypes with variation in longitudinal growth curves for traits related to obesity and body fat distribution, such as body mass index, % body fat, and various skinfolds. By targeting genes known to be involved in the development of body size and composition, we will significantly increase our understanding of the genetic factors that contribute to interindividual variation in growth and body fat distribution. Our analyses may also help identify genetic variants that may predispose some individuals toward obesity.

描述（由申请人提供）：肥胖越来越多地被认为是一个主要的公共卫生问题，这表明年轻人患病率令人震惊。虽然环境因素（例如高脂饮食和缺乏运动）占了这种兴起的大部分，但即使饮食和活动水平相似，遗传差异也可能使某些人比其他人更容易肥胖。肥胖通常在儿童期，尤其是青春期具有起源，当时体内脂肪量和分布之间的差异在青春期期间趋于发展。因此，重要的是要了解在此期间影响生长，发育和身体成分的因素。我们将通过使用先前在Project Heartbeat！过程中收集的数据和生物样本来研究在青春期影响生长和体内脂肪沉积的遗传因素，这是对儿童和青春期期间心血管疾病危险因素发展的纵向研究。在两个得克萨斯州的社区中，每年在4年的时间内测量了8-18岁的小学生3次，涵盖了青春期通常发生的时代，并且通常会发展成人身体习惯。在8、11或14岁时招募受试者，以建立3个单独的队列，随着研究的进行，这些人群会重叠，并允许构建一个涵盖参与者的整个10岁年龄范围的合成队列。样本包括136名非裔美国人（70名女性）和506名非西班牙裔白人（250名女性），平均每受试者进行8.6次检查。在每个个体中，我们将在来自生长和发育重要的激素系统中的80个基因中基因型多种单核苷酸多态性（SNP），强调已知或怀疑会影响体型和体内脂肪分布的基因。在每个基因中，将键入所有启动子区域和外显子SNP，以及通过3种不同算法在公共数据库中标识的单倍型标记的SNP。将使用三阶段算法来识别SNP的子集，其中多级混合模型将用于分析单个变体和多焦点单倍型与纵向生长曲线的变化的相关性，这些特征与肥胖和体内脂肪分布相关的特征（例如体重荷属脂肪，％脂肪脂肪，％facte）和各种skinfolds。通过靶向已知参与体型和组成发展的基因，我们将显着提高我们对有助于生长和体内脂肪分布的个体差异的遗传因素的理解。我们的分析也可能有助于确定可能使某些人倾向于肥胖的遗传变异。