IRAS FAMILY STUDY EXAMINATION-2

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。目的：启动导致肥胖和葡萄糖稳态的基因定位克隆，这是IRAS家族研究基线检查中评估的主要表型。研究计划：这个组成部分的主要目标是重新检查IRAS家族研究队列，通过收集增加我们基线数据深度的表型，获得对肥胖症和血糖稳态的遗传基础的新的生物学见解，并获得用于解释和分析主要表型的行为数据。基线数据的收集提供了重要的横断面遗传和流行病学见解；然而，为了加强对研究结果的生物学解释，特别是关于肥胖和血糖稳态措施的变化，因为它们与遗传因素、脂肪细胞因子和环境调节剂有关，需要有针对性的后续数据收集。方法：所有在1999年10月至2002年3月期间参加IRAS家系研究临床检查的基线表型部分的家庭成员将被联系参加这次后续检查。后续检查将在初次检查后约5年进行。通过我们与参与者的年度接触，应该提高后续考试的参与度。参与者将到他们原来的临床中心进行两个小时的检查，检查包括下面和附录1中描述的措施。在知情同意后，训练有素的技术人员将获得空腹血液和尿样，进行人体测量，并测量静息血压。面谈将由训练有素的面试者进行。全身DXA扫描将在诊所进行。腹部CT扫描将按照与基线检查相同的方案在非现场位置进行。对于不愿意或不能参加后续临床检查的参与者，将获得体重和糖尿病状况的自我报告。临床意义：哺乳动物基因分型服务(MGS)已经完成了从家庭成员(约2000人)收集的DNA样本的基因组扫描。连锁分析已经确定了与肥胖和葡萄糖稳态表型相关的基因组区域。连锁结果激发了分子遗传学方法的后续研究。

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. OBJECTIVE: Initiate positional cloning of genes contributing to adiposity and glucose homeostasis, the primary phenotypes evaluated in the IRAS Family Study baseline examination. RESEARCH PLAN: The primary goals of this component, the re-examination of the IRAS Family Study cohort, are to obtain new biological insights into the genetic basis of adiposity and glucose homeostasis by collection of phenotypes that add depth to our baseline data and to obtain behavioral data for interpretation and analysis of the primary phenotypes. The collection of the baseline data provided important cross-sectional genetic and epidemiologic insights; however, to enhance the biological interpretation of the study findings, particularly with respect to change in adiposity and glucose homeostasis measures as they related to genetic factors, adipocytokines and environmental modifiers, targeted follow-up data collection is required. METHODS: All family members who participated in the baseline phenotyping portion of the IRAS Family Study clinical examination between October 1999 and March 2002 will be contacted to participate in this follow-up examination. The follow-up examination will occur approximately 5 years after the initial examination. Participation in the follow-up exam should be enhanced by our annual contact with our participants. Participants will report to their original clinical center for a two-hour examination that includes the measures described below and in Appendix 1. After informed consent, trained technicians will obtain fasting blood and urine samples, will perform anthroptometry and will measure resting blood pressure. Interviews will be administered by trained interviewers. Whole body DXA scans will be performed in the clinic. The abdominal CT scan will be performed at an off-site location following the same protocol as the baseline examination. For participants unwilling or unable to attend a follow-up clinic examination, self-report of weight and diabetes status will be obtained. CLINICAL RELEVANCE: The Mammalian Genotyping Service (MGS) has completed a genome scan of the DNA samples collected from the family members (approximately 2000 individuals). Linkage analyses have identified genomic regions related to adiposity and glucose homeostasis phenotypes. The linkage results have motivated follow-up by molecular genetic approaches.