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: 8094791
• 负责人: Dana L Duren
• 金额: $ 8.23万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8094791
• 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; Only Child; Persons; Phenotype; Population; Probability; Public Health; Quantitative Genetics; Quantitative Trait Loci; Regulation; Research Personnel; Resources; Sampling Studies; Sex Characteristics; Skeletal system; Skeleton; Staging; Testing; Thick; Time; Variant; Visit; Weight; Wrist; Youth; aging gene; base; bone; bone mass; bone strength; critical period; data management; design; digital; early childhood; gene discovery; genetic analysis; genetic linkage; genetic linkage analysis; genetic pedigree; programs; sex; skeletal; skeletal tissue; success; trait; young adult

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大骨骼的积累和维护。儿童期骨骼质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，而另一些因素是通过生长和发育的其他方面介导的，例如体型的增加或骨骼成熟的速度。由于许多成人疾病的童年时期有重要的童年，包括在成年期间可能在不同时间表现出来的骨骼系统的疾病，因此更好地了解影响儿童期间造骨的因素。其中最重要的是对骨骼健康（质量和力量）度量的直接遗传影响，以及对小儿骨骼健康的相关躯体和成熟影响。提出的研究利用了FELS纵向研究中的广泛而独特的连续儿童骨骼质量，体细胞和成熟数据，以及最先进的统计和分子遗传学方法，以鉴定与骨骼质量积累有关的基因，并确定基因对基因对儿科骨架质量质量的多种毒素效应的影响。拟议的研究的最终目标是在体细胞生长和骨骼成熟的背景下确定与小儿骨骼健康有关的基因。这将通过四个特定目标来完成：AIM 1将建立一个表征小儿骨骼质量和强度的表型数据集，并同时衡量童年临界骨骼建设期间的体细胞生长和骨骼成熟。骨骼数据将从1,025名220个家庭中的1,025名儿童现有的16,000张手动X光片收集。对于每次X射线访问，可以从Fels纵向研究数据集获得体细胞数据（身高，体重和BMI）和骨骼时代的评估。 AIM 2的目的是进行定量遗传分析，以确定骨骼质量和骨骼生长和骨骼成熟度的遗传性和遗传相关性的遗传性和遗传相关性。 AIM 3的目的是通过遗传连锁，染色体区域（定量性状基因座； QTL），该区域具有负责儿童期间骨骼质量积累的基因，同时考虑了体细胞生长和骨骼成熟的指标。最后，AIM 4的目标是基于AIM 3中识别的QTL发现的基因发现。拟议的研究将对童年和成年期关键时期的骨骼建筑的遗传结构进行详尽的了解。在公共卫生方面，拟议的研究的目标尤其及时。小儿骨骼健康的重要性被认为是至关重要的，不仅对儿童健康，而且在生活的后期阶段。鉴定骨骼健康的任何共同遗传病因，童年时期的体细胞生长和成熟对于评估儿童和成人的骨骼健康至关重要。