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
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.
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