Genetics of Adiposity and Glucose Homeostasis

肥胖和血糖稳态的遗传学

基本信息

批准号：
7540880
负责人：
JILL M NORRIS
金额：
$ 13.95万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-01 至 2011-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): 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 sampledintravenous 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-alpha 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.

描述（由申请人提供）：IRAS家庭研究最初由1999年的六个链接R01资助，是一个多中心项目，旨在研究肥胖和葡萄糖稳态的遗传流行病学。在三个临床中心已经完成了招聘和表型组件。所有家庭都是非裔美国人或西班牙裔下降的家庭。已经研究了总共研究了132个扩展家庭（1861名受试者），用于使用胰岛素修饰的腹部CT扫描和葡萄糖稳态来测量肥胖，经常经常采样葡萄糖耐受性测试（FSIGT）。这些研究已经确定了对肥胖度量（内脏和皮下脂肪，BMI和腰围）的实质性贡献，以及葡萄糖稳态（胰岛素敏感性，葡萄糖有效性，急性胰岛素对葡萄糖的反应，对葡萄糖的反应，刻度指数，葡萄糖和禁食胰岛素）。 IRAS家族研究DNA的10厘米基因组扫描已经完成。连锁分析已经确定了与肥胖和葡萄糖稳态有关的几个基因组区域。这些信号中的几个已通过精细的映射进行了跟进。这种名为肥胖和葡萄糖稳态的遗传学的更新应用针对基因组区域的进一步探索以及基因的位置克隆，导致肥胖和葡萄糖稳态变化。将确定位置候选基因。我们还将重新连接原始的队列，以重复一些主要表型，以进行变化（腹部CT扫描和禁食胰岛素），并添加几种重要的新表型，以增加对我们对肥胖和葡萄糖稳态的评估的深度（DXA和脂肪细胞的总体内脂肪（包括脂肪细胞因子），包括脂肪细胞和溶剂蛋白脂肪素，包括脂肪蛋白和2NF-ulbleBlebleTf-a和2。将评估一组营养，饮食和饮食行为，以研究遗传作用。使用现有的基因组扫描数据和基于方差的链接分析方法，将检测到基因组的区域，这些区域有助于这些新表型和变化表型的变化。拟议的研究在多种族裔（非多数）样本中的肥胖性和葡萄糖稳态的发现方面是独一无二的，同时研究了这些和其他代谢表型之间的遗传和环境相关性。