GENETICS OF BONE DENSITY IN MEXICAN AMERICANS - CONTINUATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是之前的一项研究(圣安东尼奥家庭骨质疏松症研究，简称SAFOS)的延续，该研究在1997-2001年间与圣安东尼奥家庭心脏研究(SAFHS)一起，从34个家庭招募了897人。从SAFOS研究的结果中，发现了前臂骨密度(BMD)与染色体4p上的一个区域(多点Lod评分=4.8)相关联的强有力证据。还观察到骨密度增加与糖尿病和血清胰岛素水平之间的关系，尽管后一种关系并不独立于肥胖。在40岁及以上的女性中，颈动脉壁增厚(动脉粥样硬化的一种亚临床指标)与骨密度之间也观察到了强烈的正相关，尽管在男性中也检测到了显著的相关性，但方向相反。 这项研究旨在招募950名已经在SAFHS注册的受试者，他们将回国进行为期10年的访问。大多数人还将参加第一项SAFOS研究，其中包括骨矿密度的测量。将重新测量BMD，以使调查人员能够确定BMD在五年内是否发生了变化。据推测，血清胰岛素水平将与五年内骨密度的变化呈正相关，氧化低密度脂蛋白浓度将是诱发骨质疏松和亚临床动脉粥样硬化的共同危险因素。将进行五年变化的基因组扫描，预计将确定与这一特征有关的多个联系，其中一些将与先前被证明与BMD基线测量有关的基因座重叠，另一些先前未被确定为与BMD有关。将启动分子研究，目标是精细定位4号染色体上被确认与骨密度有关的QTL。为了开始这项工作，研究人员将识别位置候选基因中映射到关联区域的SNPs并对其进行基因分型，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有关。他们还将进行遗传学研究，包括确定是否有任何数量性状基因座影响骨密度的变化率。

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.