Genetics of Adiposity and Glucose Homeostasis

IRAS家族研究最初于1999年作为6个相关R 01获得资助，是一个多中心项目，旨在 研究肥胖症和葡萄糖稳态的遗传流行病学。招募和表型分析 已在三个临床中心完成。所有家庭都是非洲裔美国人或 西班牙裔共对132个大家庭（1861名受试者）进行了研究，以测量 通过腹部CT扫描和使用胰岛素修饰的频繁采样的葡萄糖稳态来评估肥胖 静脉葡萄糖耐量试验（FSIGT）。这些研究已经发现了大量的基因 对肥胖测量（内脏和皮下脂肪、BMI和腰围）的贡献， 葡萄糖稳态（胰岛素敏感性，葡萄糖有效性，对葡萄糖的急性胰岛素反应， 处置指数、空腹血糖和空腹胰岛素）。IRAS家族研究DNA的10 cM基因组扫描 已完成连锁分析已经确定了几个与肥胖相关的基因组区域， 葡萄糖稳态对其中几个信号进行了精细测绘。 这项更新申请，题为遗传学的肥胖和葡萄糖稳态，目标进一步 探索基因组区域和定位克隆有助于肥胖变异的基因， 葡萄糖稳态将鉴定位置候选基因。我们也会重新联系 重复一些主要表型以测量变化（腹部CT扫描和空腹胰岛素） 并增加了几个重要的新表型，以增加我们对肥胖和葡萄糖的评估的深度 体内平衡（DXA测定的全身脂肪和脂肪细胞因子，包括脂联素和可溶性TNF-α受体 1和2）。一组营养、饮食和饮食行为将被评估，以研究遗传学。 方面的影响.利用现有的基因组扫描数据和基于方差分量的连锁分析方法， 基因组的区域将被检测到，有助于这些新的表型的变化， 改变表型这项研究的独特之处在于它发现了肥胖症， 多种族（非多数）样本中的葡萄糖稳态，同时检查遗传和 这些和其他代谢表型之间的环境相关性。

The IRAS Family Study, initially funded as six linked R01s in 1999, is a multicenter project designed to study the genetic epidemiology of adiposity and glucose homeostasis. The recruitment and phenotyping components have been completed in the three clinical centers. All families were of African-American or Hispanic descent. A total of 132 extended families (1861 subjects) have been studied for measurement of adiposity by abdominal CT scan and glucose homeostasis using the insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT). These investigations have identified substantial genetic contribution to measures of adiposity (visceral and sub-cutaneous fat, BMI and waist circumference) and glucose homeostasis (insulin sensitivity, glucose effectiveness, acute insulin response to glucose, disposition index, fasting glucose and fasting insulin). A 10 cM genome scan of the IRAS Family Study DNA has been completed. Linkage analyses have identified several genomic regions related to adiposity and glucose homeostasis. Several of these signals have been followed-up with fine mapping. This renewal application, entitled Genetics of Adiposity and Glucose Homeostasis, targets the further exploration of genomic regions and positional cloning of genes contributing to variation in adiposity and glucose homeostasis. Positional candidate genes will be identified. We will also re-contact the original cohort to repeat some of the primary phenotypes for measures of change (abdominal CT scan and fasting insulin) and add several important new phenotypes to add depth to our assessment of adiposity and glucose homeostasis (total body fat by DXA and adipocytokines, including adiponectin and soluble TNF-a receptors 1 and 2). A panel of nutritional, dietary, and eating behaviors will be assessed in which to study the genetic effects. Using the existing genome scan data and variance-components-based linkage analysis methods, regions of the genome will be detected that contribute to variation in these new phenotypes and in the change phenotypes. The proposed study is unique in its performance of gone discovery for adiposity and glucose homeostasis in a multi-ethnic (non-majority) sample while simultaneously examining the genetic and environmental correlations among these and other metabolic phenotypes.