GENETICS OF SEX EFFECTS ON BONE DENSITY AND TURNOVER

性别遗传学对骨密度和更新的影响

• 批准号: 7349837
• 负责人: LORENA M HAVILL
• 金额: $ 1.07万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349837
• 关键词: GENETICS; SEX; EFFECTS; BONE; DENSITY

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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。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，影响着 1010 万人，其中 77% 是女性。我们迫切需要了解产生这种复杂表型和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，是基因与环境之间复杂相互作用的结果。面积骨矿物质密度 (aBMD) 提供了当前骨骼质量的测量值，而骨转换的血清测量值则反映了个体在任何时刻发生的骨形成和吸收的程度。 aBMD 和骨转换的生化标志物单独或一起使用，是骨折风险的有效预测因子。研究一致表明遗传对这些表型有很强的影响。识别包含导致这些影响的基因的染色体区域，并了解相关基因型与环境（GxE）的相互作用对于制定方案至关重要，以确定骨折风险最大的个体，这些个体可能从早期干预中受益最多。 本研究的总体目标是检测和表征基因型与“性别”、“年龄”和“繁殖史”之间的相互作用对狒狒系系 BMD 和骨转换的影响。数据包括 BMD 测量、骨转换血清标记、临床和繁殖史、331 个高度多态性微卫星标记位点的基因型以及狒狒全基因组连锁图。本研究的具体目的是： 1) 检测并表征性别、年龄和女性生殖史变量对骨密度面积和血清骨转换指标表型变异的影响； 2) 量化基因型按性别、基因型按年龄和基因型按繁殖历史变量相互作用对正常数量变化 n aBMD 和骨转换血清测量的影响，以及 3) (a) 评估先前定位于这些狒狒中的骨相关数量性状位点 (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 筛选来定位负责检测到的 GxE 效应的新 QTL。