GENETIC, SOMATIC AND MATURATIONAL INFLUENCES ON PEDIATRIC SKELETAL HEALTH

遗传、躯体和成熟对儿童骨骼健康的影响

• 批准号: 7300002
• 负责人: Dana L Duren
• 金额: $ 30.15万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-25 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7300002
• 关键词: Accounting; Adolescent; Adult; Affect; Age; Architecture; Arts; Biomechanics; Birth; Body Size; Body mass index; Body measure procedure; Bone Tissue; Candidate Disease Gene; Child; Child health care; Childhood; Collection; Computer software; Data; Data Files; Data Set; Development; Disease; Dissection; Environmental Risk Factor; Extended Family; Family; Fracture; Generations; Genes; Genetic; Genetic Predisposition to Disease; Genome; Goals; Growth; Growth and Development function; Hand; Health; Height; Heritability; Individual; Knowledge; Length; Life; Longitudinal Studies; Maintenance; Measures; Mediating; Metacarpal bone; Methods; Modeling; Molecular Genetics; Nature; Nuclear; Nucleotides; Numbers; Only Child; Persons; Phenotype; Population; Probability; Public Health; Quantitative Genetics; Quantitative Trait Loci; Rate; Regulation; Research Personnel; Resources; Sampling Studies; Sex Characteristics; Skeletal system; Skeleton; Staging; Testing; Thick; Time; Tissues; Variant; Visit; Weight; Wrist; Youth; aging gene; base; bone; bone health; bone strength; critical developmental period; data management; design; digital; early childhood; gene discovery; genetic analysis; genetic linkage; genetic linkage analysis; genetic pedigree; programs; sex; success; trait

DESCRIPTION (provided by applicant): A fundamental aspect of childhood growth and development is the buildup and maintenance of a strong skeleton. The regulation of skeletal mass during childhood is influenced by genetic and environmental factors. Some of these factors act directly upon the skeleton, while others are mediated through other aspects of growth and development such as increases in body size or the tempo of skeletal maturation. Because there are significant childhood antecedents to many adult diseases, including those of the skeletal system that can manifest at different times during adulthood, it is important to better understand the factors affecting bone-building during childhood. Foremost among these are direct genetic influences on measures of skeletal health (mass and strength), and associated somatic and maturational influences on pediatric skeletal health. The proposed study leverages extensive and unique serial childhood skeletal mass, somatic and maturation data from the Fels Longitudinal Study, and state-of-the-art statistical and molecular genetic approaches, to identify genes involved in the accumulation of skeletal mass, and to identify possible pleiotropic effects of genes on pediatric skeletal mass, body habitus, and skeletal maturation. The ultimate goal of the proposed study is to identify genes involved in pediatric skeletal health in the context of somatic growth and skeletal maturation. This will be accomplished through four specific aims: Aim 1 will establish a phenotypic dataset characterizing pediatric skeletal mass and strength, with concurrent measures of somatic growth and skeletal maturation during critical bone-building periods of childhood. Skeletal data will be collected from over 16,000 existing hand radiographs from 1,025 children in 220 families. For each x-ray visit, somatic data (height, weight, and BMI) and assessments of skeletal age are available from the Fels Longitudinal Study dataset. The goal of Aim 2 is to conduct quantitative genetic analyses to identify the heritability of, and genetic correlations between, skeletal mass and measures of somatic growth and skeletal maturation over the course of childhood. The goal of Aim 3 is to identify, through genetic linkage, chromosomal regions (quantitative trait loci; QTL) harboring genes responsible for the accumulation of skeletal mass during childhood, while simultaneously accounting for measures of somatic growth and skeletal maturation. Finally, the goal of Aim 4 is gene discovery based on QTL identified in Aim 3. The proposed study will provide a thorough understanding of the genetic architecture of bone- building during the critical periods of childhood and young adulthood. In terms of public health, the goals of the proposed study are particularly timely. The importance of pediatric skeletal health is becoming recognized as critical, not only for child health, but also during later stages of life. The identification of any shared genetic etiology of skeletal health, somatic growth and maturation during childhood may prove critical for the assessment of skeletal health in children and adults.

描述（由申请人提供）：儿童成长和发展的一个基本方面是强壮骨骼的建立和维护。儿童时期骨量的调节受遗传和环境因素的影响。其中一些因素直接作用于骨骼，而另一些则通过生长和发育的其他方面（如体型的增加或骨骼成熟的速度）进行调节。由于许多成人疾病，包括在成年期不同时间出现的骨骼系统疾病，在童年时期都有重要的先兆，因此更好地了解儿童时期影响骨骼发育的因素是很重要的。其中最重要的是对骨骼健康（质量和力量）测量的直接遗传影响，以及对儿童骨骼健康相关的躯体和成熟影响。本研究利用来自费尔斯纵向研究的广泛而独特的儿童骨量、躯体和成熟数据，以及最先进的统计和分子遗传学方法，确定参与骨量积累的基因，并确定基因对儿童骨量、身体习惯和骨骼成熟的可能的多效性影响。提出的研究的最终目的是确定在躯体生长和骨骼成熟的背景下参与儿童骨骼健康的基因。这将通过四个具体目标来实现：目标1将建立表征儿童骨骼质量和强度的表型数据集，并同时测量儿童期关键骨骼构建时期的躯体生长和骨骼成熟。骨骼数据将从220个家庭的1,025名儿童的16,000多张现有手部x光片中收集。对于每次x光检查，身体数据（身高、体重和BMI）和骨骼年龄评估可从费尔斯纵向研究数据集中获得。Aim 2的目标是进行定量遗传分析，以确定儿童期骨骼质量与躯体生长和骨骼成熟测量之间的遗传相关性。Aim 3的目标是通过遗传连锁，确定染色体区域（数量性状位点；QTL），其中包含负责儿童期骨骼质量积累的基因，同时考虑到体细胞生长和骨骼成熟的措施。最后，Aim 4的目标是基于Aim 3中鉴定的QTL发现基因。提出的研究将提供在儿童和青年成年的关键时期骨建设的遗传结构的透彻理解。就公共卫生而言，拟议研究的目标尤其及时。儿童骨骼健康的重要性越来越被认为是至关重要的，不仅对儿童健康，而且在生命的后期阶段。确定儿童时期骨骼健康、躯体生长和成熟的任何共同遗传病因，可能对评估儿童和成人的骨骼健康至关重要。