GENETIC OF BONE GEOMETRY: FRAMINGHAM COHORTS

骨几何遗传学：弗雷明汉队列

• 批准号: 6870066
• 负责人: DAVID KARASIK
• 金额: $ 23.53万
• 依托单位: HEBREW REHABILITATION CENTER FOR AGED
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6870066
• 关键词: GENETIC; BONE; GEOMETRY; FRAMINGHAM; COHORTS

DESCRIPTION (provided by applicant): This supplemental application is an extension of our recently funded R01 (AR050066-01), of which the primary aim is to perform a genome screen to identify multivariate linkage of bone geometry indices with a set of autosomal microsatellite markers. The primary goal of this proposed study is to test for associations of candidate genes with geometrical properties of bone. This study will take advantage of existing hand x-rays and dual x-ray absorptiometry scans of the hip from participants of the Framingham Heart Study, one of the longest running cohort studies in the world. The specific hypotheses of this supplement are: - Genetic factors explain a significant portion of variability in geometric indices that will be derived as part of this project in both the weight-bearing femur and in non weight-bearing metacarpals - Polymorphisms in genes coding for bone matrix proteins, gonadal steroids, growth factors, and cytokines, will be associated with indices of bone geometry at two skeletal sites. In the proposed study, data from both related and unrelated Framingham participants will be used to perform genetic association analyses of bone geometry indices with a number of genes that are likely to play a role in the determination of bone geometry. Our general approach will be to test an association and linkage/association between candidate genetic polymorphisms and bone geometric phenotypes, using a sample of unrelated individuals, as well as a sample of family members from Framingham. Our selection of candidate genes for this work will be determined from three main sources of information: 1) published literature, 2) expression profiling of mouse femora mechanically stimulated ex vivo, and 3) collaboration with mouse geneticists through the use of refined bone imaging data and microarray data from congenic mouse strains. Bone geometry is an important measure of bone fragility and risk of osteoporotic fractures. Elucidation of genetic and molecular mechanisms underlying bone strength will ultimately lead to the identification of the individuals at highest risk of osteoporotic fractures who can be targeted for therapeutic interventions.

描述（由申请人提供）：本补充申请是我们最近资助的R 01（AR 050066 -01）的扩展，其主要目的是进行基因组筛选，以确定骨几何指数与一组常染色体微卫星标记的多变量连锁。 这项研究的主要目的是测试候选基因与骨几何特性的关联。这项研究将利用现有的手X射线和双X射线吸收测量扫描髋关节的参与者的心脏研究，在世界上最长的运行队列研究之一。 该补充的具体假设是： - 遗传因素解释了几何指数变异的一个重要部分，这些几何指数将作为本项目的一部分在承重股骨和非承重掌骨中推导出来 - 编码骨基质蛋白、性腺类固醇、生长因子和细胞因子的基因的多态性将与两个骨骼部位的骨几何指数相关。 在拟议的研究中，将使用相关和不相关的Frachial参与者的数据对骨几何指数与可能在确定骨几何结构中发挥作用的许多基因进行遗传关联分析。我们的一般方法将是使用无关个体样本以及来自Frachial的家族成员样本来测试候选遗传多态性和骨几何表型之间的关联和连锁/关联。我们将从三个主要的信息来源中选择候选基因：1）已发表的文献，2）离体机械刺激小鼠股骨的表达谱，3）通过使用来自同类小鼠品系的精细骨成像数据和微阵列数据与小鼠遗传学家合作。 骨几何形状是衡量骨脆性和骨质疏松性骨折风险的重要指标。阐明骨强度的遗传和分子机制将最终导致识别出可作为治疗干预目标的最高风险的骨质疏松性骨折个体。