GENETICS OF SEX EFFECTS ON BONE DENSITY AND TURNOVER

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。骨质疏松症和相关的骨骼脆弱性是最重要的公共卫生问题，影响了1010万人，其中77%是妇女。迫切需要了解产生这种复杂表型和这种性别差异的生物学机制。低骨量是骨质疏松症易感性的最可靠指标，是基因和环境之间复杂相互作用的结果。面积骨密度(ABMD)提供了当前骨骼质量的测量，而血清骨转换测量反映了个体在任何时候发生的骨形成和吸收的程度。骨密度和骨转换生化标记物单独或联合使用是预测骨折风险的有效指标。研究一直表明，这些表型具有很强的遗传效应。确定含有导致这些影响的基因的染色体区域，并了解相关的基因与环境(GxE)的相互作用，对于制定协议以确定谁可能从早期干预中受益最大的骨折风险最大的个体至关重要。这项研究的总体目的是检测和描述性别、年龄和生殖史之间的交互作用对狒狒家系的骨密度和骨转换的影响。数据包括骨密度测量，骨转换的血清标记物，临床和生殖史，331个高度多态的微卫星标记基因座的基因类型，以及狒狒全基因组连锁图。这项研究的具体目的是：1)检测和表征性别、年龄和雌性生殖史变量对面积骨密度和血清骨转换指标表型变异的影响；2)量化不同性别、不同年龄和不同生殖历史变量交互作用对正常骨密度和血清骨转换指标数量变异的影响；以及3)(A)评估先前定位在这些狒狒中的骨相关数量性状基因座(QTL)对检测到的GxE相互作用的影响，以及(B)进行全基因组连锁筛选，以定位新的负责检测到GxE效应的QTL。

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. Osteoporosis and associated skeletal fragility are paramount public health concerns, affecting 10.1 million individuals, 77% of whom are women. The need to understand the biological mechanisms producing this complex phenotype and this sex difference is immediate. Low bone mass, the most reliable indicator of osteoporosis susceptibility, results from complex interactions between genes and environment. Areal bone mineral density (aBMD) provides a measure of current skeletal mass, while serum measures of bone turnover reflect the degree of bone formation and resorption occurring in an individual at any one time. aBMD and biochemical markers of bone turnover, used alone and together, are effective predictors of fracture risk. Studies consistently show strong genetic effects on these phenotypes. Identifying chromosomal regions harboring genes responsible for these effects, and understanding relevant genotype-by-environment (GxE) interactions are essential for the development of protocols to identify individuals at greatest risk for fracture who might benefit most from early intervention. The overall aim of this research is to detect and characterize effects of interactions between genotype and ¿sex, -age, and ¿reproductive history on BMD and bone turnover in pedigreed of baboons. Data include measures of BMD, serum markers of bone turnover, clinical and reproductive histories, genotypes at 331 highly polymorphic microsatellite marker loci, and a baboon whole genome linkage map. The specific aims of this research are to: 1) detect and characterize the effects of sex, age, and female reproductive history variables on the phenotypic variance in area BMD and serum measures of bone turnover; 2) Quantify the effects of genotype-by-sex, genotype-by-age, and genotype-by-reproductive history variable interactions on normal quantitative variation n aBMD and serum measures of bone turnover, and 3) (a) assess the effects of bone-related quantitative trait loci (QTLs), previously localized in these baboons, on detected GxE interactions and (b) conduct whole genome linkage screens to localize new QTLs responsible for detected GxE effects.