GENETICS OF BONE DENSITY IN MEXICAN AMERICANS - CONTINUATION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是先前研究（圣安东尼奥家庭骨质疏松症研究，或SAFOS）的延续，该研究与圣安东尼奥家庭心脏研究（SAFHS）一起，在1997-2001年期间招募了来自34个家庭的897名个体。从SAFOS研究的结果中，强有力的证据表明前臂骨矿物质密度（BMD）与染色体4p上的一个区域有关联（多点负荷评分= 4.8）。骨密度增加与糖尿病和血清胰岛素水平之间也存在关联，尽管后者并非独立于肥胖。此外，在40岁及以上的女性中，颈动脉壁增厚（动脉粥样硬化的亚临床指标）与骨密度之间也存在很强的正相关，尽管在男性中也发现了显著的相关性，但方向相反。本研究旨在招募950名已经加入SAFHS的受试者，他们将返回进行为期10年的访问。大多数人也将参加第一次SAFOS研究，其中包括骨矿物质密度的测量。将重新测量骨密度，使研究人员能够确定骨密度是否在五年内发生变化。假设血清胰岛素水平与BMD的五年变化呈正相关，氧化LDL浓度将是骨质疏松症和亚临床动脉粥样硬化的常见危险因素。将进行五年变化的基因组扫描，预计将确定与该特征的多个联系，其中一些将与先前显示与BMD基线测量相关的位点重叠，而其他先前未确定与BMD相关的位点重叠。分子研究将启动，目标是精确定位4号染色体上与BMD相关的QTL。为了开始这项工作，研究人员将在定位的候选基因中识别和基因型snp，并将进行关联分析，以检测过去五年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，包括确定是否有任何数量性状位点影响骨矿物质密度的变化率。

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.