GENETICS OF BONE DENSITY IN MEXICAN AMERICANS - CONTINUATION

墨西哥裔美国人的骨密度遗传学 - 续

• 批准号: 7627493
• 负责人: JAN M BRUDER
• 金额: $ 3.24万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627493
• 关键词: Age; Atherosclerosis; Bone Density; Candidate Disease Gene; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 4; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Enrollment; Family; Forearm; Funding; Genetic; Genome Scan; Goals; Grant; Heart; Hyperinsulinism; Individual; Institution; Insulin; Link; Linkage Disequilibrium; Lod Score; Maps; Measurement; Measures; Mexican Americans; Molecular; Obesity; Osteoporosis; Quantitative Trait Loci; Rate; Research; Research Personnel; Resources; Risk Factors; SNP genotyping; Serum; Source; United States National Institutes of Health; Visit; Woman; cardiovascular risk factor; men; oxidized low density lipoprotein; trait; Age; Atherosclerosis; Bone Density; Candidate Disease Gene; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 4; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Enrollment; Family; Forearm; Funding; Genetic; Genome Scan; Goals; Grant; Heart; Hyperinsulinism; Individual; Institution; Insulin; Link; Linkage Disequilibrium; Lod Score; Maps; Measurement; Measures; Mexican Americans; Molecular; Obesity; Osteoporosis; Quantitative Trait Loci; Rate; Research; Research Personnel; Resources; Risk Factors; SNP genotyping; Serum; Source; United States National Institutes of Health; Visit; Woman; cardiovascular risk factor; men; oxidized low density lipoprotein; trait

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a continuation of a previous study (San Antonio Family Osteoporosis Study, or SAFOS) which enrolled 897 individuals from 34 families from 1997-2001, in conjunction with the San Antonio Family Heart Study (SAFHS). From the results of the SAFOS study, strong evidence was detected for linkage of forearm bone mineral density (BMD) to a region on chromosome 4p (multipoint lod score = 4.8). Associations were also observed between increased BMD with both diabetes and serum insulin levels, although this latter correlation as not independent of obesity. Also observed was a strong positive correlation between carotid wall thickening, a subclinical measure of atherosclerosis, and BMD in women ages 40 years and older, although in men a significant correlation was also detected but in the opposite direction. This study seeks to enroll 950 subjects already enrolled in the SAFHS who will be returning for their 10-year visit. Most will have also been enrolled in the first SAFOS study, which included measurement of bone mineral density. BMD will be re-measured to enable investigators to determine whether there has been a change in BMD over five years. It is hypothesized that serum insulin levels will be positively correlated with five-year change in BMD, and that oxidized LDL concentrations will be a common risk factor predisposing subjects to both osteoporosis and subclinical atherosclerosis. A genome scan of five-year changes will be performed, and it is anticipated that multiple linkages to this trait will be identified, some of which will overlap with loci previously shown to be linked to the baseline measure of BMD, and others not previously identified as being linked to BMD. Molecular studies will be initiated, with the goal of fine-mapping the QTL on chromosome 4 identified as being linked to BMD. To begin this effort, investigators will identify and genotype SNPs within positional candidate genes that map to the linked region and will perform association analyses to detect whether linkage disequilibrium over the previous five years are associated with hyperinsulinemia or cardiovascular risk factors. They will also perform genetic studies, including determining whether any quantitative trait loci influence the rate of change of bone mineral density.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 这是一项先前的研究（圣安东尼奥家族骨质疏松研究或SAFOS）的延续，该研究与圣安东尼奥家庭心脏研究（Safhs）一起招募了来自1997 - 2001年34个家庭的897名个人。 从SAFOS研究的结果中，发现了有力的证据表明前臂骨矿物质密度（BMD）与4p染色体上的区域（多点LOD得分= 4.8）上的区域。 在糖尿病和血清胰岛素水平增加的BMD之间也观察到了关联，尽管后者的相关性并非与肥胖无关。 还观察到的是颈动脉壁增厚，动脉粥样硬化的亚临床量度和40岁以上女性的BMD之间的强正相关，尽管在男性中也检测到显着的相关性，但在相反方向上。 这项研究旨在招募950名已经入学的SAFH，他们将返回10年的访问。 大多数人也将参加了首次SAFOS研究，其中包括测量骨矿物质密度。 BMD将被重新测量，以使研究人员能够确定BMD是否在五年内发生了变化。 假设血清胰岛素水平将与BMD的五年变化呈正相关，并且氧化的LDL浓度将是常见的危险因素诱发骨质疏松症和亚临床动脉粥样硬化。 将进行五年变化的基因组扫描，预计将确定与该性状的多个联系，其中一些将与先前显示的基因座重叠，该基因座先前显示与BMD的基线量度相关，而其他未经确定为链接到BMD的基础措施。 将启动分子研究，目的是在4号染色体上绘制QTL，该染色体被确定为与BMD相关的QTL。 为了开始这项工作，研究人员将在位置候选基因中识别和基因型SNP，这些基因映射到链接区域，并将进行关联分析，以检测前五年中的连锁不平衡是否与高胰岛素血症或心血管危险因素有关。 他们还将进行遗传研究，包括确定任何定量性状基因座是否影响骨矿物质密度的变化率。