Genetics of Adiposity and Glucose Homeostasis

肥胖和血糖稳态的遗传学

• 批准号: 7497191
• 负责人: Lynne E Wagenknecht
• 金额: $ 5.3万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-15 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497191
• 关键词: 12q; 17q21; 17q24; 6p23; Abdomen; Accounting; Acute; Address; Adipose tissue; African American; Behavior; Body fat; Candidate Disease Gene; Chronic Disease; Clinical; Collaborations; Communities; Cutaneous; DNA; Data; Depth; Diet; Dual-Energy X-Ray Absorptiometry; Eating Behavior; Effectiveness; Environmental Risk Factor; Extended Family; Family; Family Study; Family member; Fasting; Fatty acid glycerol esters; Funding; Future; Genes; Genetic; Genetic Markers; Genetic Variation; Genome; Genome Scan; Genomics; Genotype; Glucose; Haplotypes; Hispanics; Individual; Insulin; Insulin Resistance; Interleukin-6; Investigation; Leptin; Link; Linkage Disequilibrium; Manuscripts; Maps; Measurement; Measures; Metabolic; Methods; Minority; Molecular; Molecular Analysis; Molecular Genetics; Nonesterified Fatty Acids; Nutritional; Obesity; Other Genetics; Performance; Phenotype; Physical activity; Population; Population Genetics; Principal Investigator; Productivity; Publications; Quantitative Trait Loci; Research Personnel; Risk Factors; Role; SNP genotyping; Sampling; Services; Signal Transduction; Single Nucleotide Polymorphism Map; Source; Structure; Study Subject; Surveys; Tumor Necrosis Factor Receptor; Variant; Visceral; Waist-Hip Ratio; X-Ray Computed Tomography; abdominal fat; adiponectin; base; blood glucose regulation; cohort; density; design; disorder risk; follow-up; gene discovery; gene environment interaction; genetic analysis; genetic epidemiology; genetic linkage analysis; genetic pedigree; indexing; insulin secretion; insulin sensitivity; intravenous glucose tolerance test; novel; positional cloning; programs; receptor; response; subcutaneous; success; trait; waist circumference

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.

IRAS家庭研究最初于1999年由6个相关的r01资助，是一个多中心项目，旨在