GENETICS OF BONE DENSITY IN MEXICAN AMERICANS - CONTINUATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这是先前研究（圣安东尼奥家庭骨质疏松研究，或SAFOS）的延续，该研究从1997-2001年招募了来自34个家庭的897名个体，并与圣安东尼奥家庭心脏研究（SAFHS）结合。 从SAFOS研究的结果中，检测到前臂骨矿物质密度（BMD）与染色体4p上的一个区域（多点lod评分= 4.8）连锁的强有力证据。 还观察到BMD增加与糖尿病和血清胰岛素水平之间的关联，尽管后者的相关性与肥胖无关。 还观察到颈动脉壁增厚，动脉粥样硬化的亚临床指标，和BMD之间的强正相关性在40岁及以上的女性，虽然在男性中也检测到显着的相关性，但在相反的方向。 本研究旨在入组950例已入组SAFHS的受试者，这些受试者将返回进行10年访视。 大多数人还将参加第一项SAFOS研究，其中包括测量骨矿物质密度。 将重新测量BMD，以使研究者能够确定5年内BMD是否发生变化。 据推测，血清胰岛素水平将与BMD的五年变化呈正相关，氧化LDL浓度将是一个共同的危险因素，易患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重联系，其中一些将与先前显示与BMD基线测量相关的基因座重叠，而其他基因座先前未确定与BMD相关。 将启动分子研究，目标是对4号染色体上被鉴定为与BMD相关的QTL进行精细定位。 为了开始这项工作，研究人员将在定位到连锁区域的位置候选基因内鉴定和分型SNP，并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相关。 他们还将进行遗传研究，包括确定是否有任何数量性状基因座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.