GENETIC OF BONE STRUCTURAL GEOMETRY: FRAMINGHAM COHORTS

骨结构几何遗传学：弗雷明汉队列

• 批准号: 7118625
• 负责人: DAVID KARASIK
• 金额: $ 73.58万
• 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 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7118625
• 关键词: bone; bone density; bone imaging /visualization /scanning; clinical research; femur; genetic markers; genetic polymorphism; genetic susceptibility; human data; human genetic material tag; linkage mapping; longitudinal human study; osteoporosis; photon absorptiometry; pleiotropism; quantitative trait loci; radiography; single nucleotide polymorphism

DESCRIPTION: (provided by applicant) Bone geometry is a valid measure of bone fragility and risk of osteoporotic fractures. The primary aim of this study is to identify and evaluate genes determining 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. Well-described pedigrees from the Framingham Study along with an existing genome scan, including microsatellites uniformly distributed throughout the genome, will allow us to perform a study of the genetic sources of variation in bone geometry. Elucidation of genetic and molecular mechanisms underlying bone structure and strength will ultimately lead to the identification of the individuals at highest risk of osteoporotic fractures who can be targeted for therapeutic interventions. The specific hypotheses of this study 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-beating femur and in non weight-beating metacarpals. - Significant linkage with chromosomal loci will be found for indices of bone geometry at femur and metacarpals. - Common genetic sources will be found for femoral and metacarpal indices, with pleiotropic effect also on bone mineral density of femur and quantitative ultrasound of heel that are already investigated as part of the Framingham Osteoporosis Study. Initial linkage results will be refined by genotyping additional markers in genomic regions with LOD scores suggestive of linkage with femoral and metacarpal geometric indices. Our goal is to fine-tune localization of quantitative trait loci by examining polymorphic markers within these regions. Linkage analysis will also be combined with family based tests of association with candidate genes that lie under the peak, with additional mapping with single nucleotide polyrnorphisms.

描述：（由申请人提供）骨几何结构是骨脆性和骨质疏松性骨折风险的有效指标。本研究的主要目的是鉴定和评估决定骨几何特性的基因。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。来自Frachial Study的良好描述的谱系沿着现有的基因组扫描，包括均匀分布在整个基因组中的微卫星，将使我们能够对骨骼几何结构变异的遗传来源进行研究。 阐明骨结构和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。 本研究的具体假设是： - 遗传因素解释了一个显着的部分几何指数的变异性，将作为本项目的一部分，在两个重量跳动的股骨和非重量跳动的掌骨。 - 显着的连锁与染色体位点将被发现在股骨和掌骨的骨几何指数。 - 将发现股骨和掌骨指数的共同遗传来源，对股骨的骨矿物质密度和足跟的定量超声也有多效性影响，这些都已作为股骨骨质疏松症研究的一部分进行了研究。 将通过对基因组区域中的其他标记物进行基因分型来完善初始连锁结果，LOD评分提示与股骨和掌骨几何指数的连锁。我们的目标是通过检查这些区域内的多态性标记来微调数量性状位点的定位。连锁分析还将与基于家族的与位于峰下的候选基因的关联测试相结合，并使用单核苷酸多态性进行额外的作图。

项目成果

Osteoporosis: an evolutionary perspective.

骨质疏松症：进化的角度。

• DOI: 10.1007/s00439-008-0559-8
• 发表时间: 2008
• 期刊: Human genetics
• 影响因子: 5.3
• 作者: Karasik,David

Refined QTLs of osteoporosis-related traits by linkage analysis with genome-wide SNPs: Framingham SHARe.

• DOI: 10.1016/j.bone.2010.01.001
• 发表时间: 2010-04
• 期刊: Bone
• 影响因子: 4.1
• 作者: Karasik D;Dupuis J;Cho K;Cupples LA;Zhou Y;Kiel DP;Demissie S
• 通讯作者: Demissie S

Genome-wide pleiotropy of osteoporosis-related phenotypes: the Framingham Study.

• DOI: 10.1002/jbmr.38
• 发表时间: 2010-07
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Karasik, David;Hsu, Yi-Hsiang;Zhou, Yanhua;Cupples, L. Adrienne;Kiel, Douglas P.;Demissie, Serkalem
• 通讯作者: Demissie, Serkalem