Genetics of Adiposity and Glucose Homeostasis

IRAS家庭研究最初于1999年作为六个相连的R01获得资助，是一个多中心项目，旨在 研究肥胖和血糖动态平衡的遗传流行病学。招募和表型分析 三个临床中心的部件已经完成。所有家庭都是非裔美国人或 西班牙裔后裔。总共对132个大家庭(1861名受试者)进行了测量 腹部CT扫描的肥胖和频繁采样的胰岛素修饰的血糖稳态 静脉葡萄糖耐量试验(FSIGT)。这些研究已经确定了大量的基因 对肥胖测量的贡献(内脏和皮下脂肪、BMI和腰围)和 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、 倾向指数、空腹血糖和空腹胰岛素)。IRAS家族研究DNA的10 cM基因组扫描 已经完成了。连锁分析已经确定了几个与肥胖症和 葡萄糖动态平衡。这些信号中的几个已经被跟踪并进行了精细的绘制。 这项名为《脂肪和葡萄糖稳态遗传学》的续订申请，目标是进一步 肥胖症和肥胖相关基因的基因组区域探索和定位克隆 葡萄糖动态平衡。位置候选基因将被识别出来。我们还将重新联系最初的同伙 重复一些主要的表型以测量变化(腹部CT扫描和空腹胰岛素) 并添加了几个重要的新表型，以增加我们对肥胖和血糖的评估的深度 动态平衡(DXA和脂肪细胞因子，包括脂联素和可溶性肿瘤坏死因子-a受体)所产生的全身脂肪 1和2)。将评估一组营养、饮食和饮食行为，在其中研究遗传 效果。使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， 将检测到基因组中导致这些新表型和 改变表型。这项拟议的研究是独一无二的，它的表现是发现肥胖和 在多种族(非多数)样本中的葡萄糖稳态，同时检测遗传和 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.