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

基因、激素、生长和体脂：心跳计划

• 批准号: 7463628
• 负责人: DAVID MICHAEL HALLMAN
• 金额: $ 29.24万
• 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/7463628
• 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; Promoter Regions; Puberty; Public Health; Range; Research Personnel; 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）：肥胖越来越被认为是一个主要的公共卫生问题，其在年轻人中的患病率呈惊人的上升趋势。虽然高脂肪饮食和缺乏运动等环境因素是导致肥胖率上升的主要原因，但遗传差异可能使某些人比其他人更容易肥胖，即使他们的饮食和活动水平相似。肥胖通常起源于儿童期，尤其是青春期，个体之间的体脂肪量和分布差异往往在青春期出现。因此，了解这一时期影响生长、发育和身体成分的因素非常重要。我们将利用之前在“心跳计划”（一项针对儿童和青春期心血管疾病危险因素发展的纵向研究）期间收集的数据和生物样本来研究影响青春期生长和身体脂肪沉积的遗传因素。在得克萨斯州的两个社区，8 至 18 岁的学童在 4 年内每年接受多达 3 次测量，涵盖青春期正常发生和成人身体习惯通常形成的年龄。受试者在 8 岁、11 岁或 14 岁入组，建立 3 个独立的队列，随着研究的进展，这些队列的年龄会重叠，并允许构建涵盖参与者整个 10 岁年龄范围的综合队列。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），每个受试者平均进行 8.6 次检查。在每个个体中，我们将对来自对生长和发育很重要的激素系统的 80 个基因中的多个单核苷酸多态性 (SNP) 进行基因分型，重点关注已知或怀疑影响体型和体脂肪分布的基因。在每个基因中，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识别的单倍型标记 SNP，都将被分型。将使用三阶段算法来识别 SNP 的子集，其中将使用多级混合模型来分析个体变异和多位点单倍型与肥胖和身体脂肪分布相关性状的纵向生长曲线变化之间的关联，例如如体重指数、体脂百分比和各种皮褶。通过针对已知参与身体尺寸和成分发育的基因，我们将显着增进对导致个体间生长和身体脂肪分布差异的遗传因素的理解。我们的分析还可能有助于识别可能导致某些人肥胖的遗传变异。