Insulin resistance is an important risk factor for atherosclerosis. There is evidence indicating that much of the variation in insulin resistance can be attributed to genetic sources. Visceral adiposity, another important risk factor for atherosclerosis, is strongly correlated with insulin resistance, and this trait also appears to be under substantial genetic control. The overall goals of the proposed research project are to: 1) identify the genetic determinants of insulin resistance and visceral adiposity; and 2) determine the extent to which insulin resistance, visceral adiposity, and metabolic cardiovascular disease risk factors share common genetic influences. To address these goals, we will enroll 160 families of African-American and Hispanic background using participants of the Insulin Resistance Atherosclerosis Study (IRAS) as index cases. Approximately 1280 additional family members will be recruited to the study for a total of 1440 participants. Insulin resistance will be measured using the frequently sampled intravenous glucose tolerance test, and visceral adiposity will be measured using computed tomography. Metabolic cardiovascular disease risk factors will also be assessed. A panel of 370 microsatellite markers will be genotyped to provide data for a genome-wide scan to detect chromosomal regions containing quantitative trait loci (QTLs) that influence phenotypic variation for insulin resistance and visceral adiposity. We will then saturate the regions of linkage identified in these analyses with additional markers and then utilize linkage disequilibrium to localize further the QTLs. The organization of this study will be similar to that of IRAS, with three clinical centers, a coordinating center, a central laboratory and a genetics laboratory. Wake Forest University will be responsible for serving as the coordinating center for the study, with the responsibility for coordinating the data collection and data management and conducting statistical analyses. This project will contribute substantially to our understanding of the genetic determinants of insulin resistance, visceral adiposity, and, consequently to risk of atherosclerosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL060944-02
Application #
6185062
Study Section
Special Emphasis Panel (ZHL1-CSR-R (M1))
Project Start
1999-08-15
Project End
2004-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
2
Fiscal Year
2000
Total Cost
$511,073
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Young, Kendra A; Maturu, Amita; Lorenzo, Carlos et al. (2018) The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of insulin resistance, ?-cell function, and diabetes in Hispanics and African Americans. J Diabetes Complications :
Gao, Chuan; Langefeld, Carl D; Ziegler, Julie T et al. (2018) Genome-Wide Study of Subcutaneous and Visceral Adipose Tissue Reveals Novel Sex-Specific Adiposity Loci in Mexican Americans. Obesity (Silver Spring) 26:202-212
Gao, Chuan; Tabb, Keri L; Dimitrov, Latchezar M et al. (2018) Exome Sequencing Identifies Genetic Variants Associated with Circulating Lipid Levels in Mexican Americans: The Insulin Resistance Atherosclerosis Family Study (IRASFS). Sci Rep 8:5603
Hong, Jaeyoung; Hatchell, Kathryn E; Bradfield, Jonathan P et al. (2018) Transethnic Evaluation Identifies Low-Frequency Loci Associated With 25-Hydroxyvitamin D Concentrations. J Clin Endocrinol Metab 103:1380-1392
Hellwege, Jacklyn N; Palmer, Nicholette D; Dimitrov, Latchezar et al. (2017) Genome-wide linkage and association analysis of cardiometabolic phenotypes in Hispanic Americans. J Hum Genet 62:175-184
Graff, Mariaelisa; Emery, Leslie S; Justice, Anne E et al. (2017) Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos. Lipids Health Dis 16:200
Lee, C Christine; Young, Kendra A; Norris, Jill M et al. (2017) Association of Directly Measured Plasma Free 25(OH)D With Insulin Sensitivity and Secretion: The IRAS Family Study. J Clin Endocrinol Metab 102:2781-2788
Wood, Andrew R; Jonsson, Anna; Jackson, Anne U et al. (2017) A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants. Diabetes 66:2296-2309
Palmer, Nicholette D; Wagenknecht, Lynne E; Langefeld, Carl D et al. (2016) Improved Performance of Dynamic Measures of Insulin Response Over Surrogate Indices to Identify Genetic Contributors of Type 2 Diabetes: The GUARDIAN Consortium. Diabetes 65:2072-80
Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa et al. (2016) Trans-ethnic Meta-analysis and Functional Annotation Illuminates theĀ Genetic Architecture of Fasting Glucose and Insulin. Am J Hum Genet 99:56-75

Showing the most recent 10 out of 43 publications