Type 2 diabetes (T2D) is a growing health problem, especially in minority race-ethnic groups. Ancestral variation in genetic background coupled with recent, rapid increases in obesity and unhealthy behavioral and social factors account for rising rates of T2D and its disparities in the U.S. The proposed research focuses on prediabetes, where intervention is known to prevent T2D, and where downstream race-ethnic disparities in T2D are suspected to begin. Phenotypic race-ethnic differences in prediabetes have been characterized, but genetic differences have not. There are strong scientific as well as ethical reasons to study race-ethnic differences in T2D genetic risk. This is a renewal of a mid-career investigator award in patient-oriented research (K24). The candidate, James B. Meigs MD MPH, has devoted his patient-oriented research career to study of the cause and prevention of type 2 diabetes. This award will support the following Specific Aims: 1. Discover, map, and characterize T2D quantitative trait-associated genetic loci in multi-ethnic population samples (African American, Hispanic, Asian and European ancestry). This will be achieved using staged genome-wide association studies with meta-analysis and with characterization of confirmed T2D quantitative trait loci using interaction, outcomes, physiology, pathway, and sequencing studies. Diabetes-related quantitative traits include levels of fasting insulin, glucose, and hemoglobin A1c;2. Translate new genetic knowledge to diverse race-ethnic samples for clinical and population health benefit using longitudinal and multilevel tests of genetic measures and social, behavioral, environmental and biophysiological measures of risk for elevated fasting glucose, prediabetes, or clinical T2D;3. Build on the candidate's successful research and mentoring program by ensuring mid-career protected time for patient-oriented research program development within the superb environment of Harvard, Massachusetts General Hospital and an extensive network of research collaborations, and by maintaining the ongoing capacity to provide mentoring to a larger number of junior patient-oriented investigators. Patient-oriented research is critical for the translation of scientific knowledge into population health benefit. T2 is a rapidly growing clinical and public health problem. This mid-career award application seeks to directly address the need for patient-oriented research and mentoring focused on the causes and consequences of T2D. Expanded knowledge of precursors of T2D is critical to identify novel approaches for prevention and control of the widening diabetes epidemic.

Public Health Relevance

Type 2 diabetes (T2D) is a growing health problem, especially in minority race-ethnic groups. The proposed research focuses on improved knowledge of prediabetes risk factors like fasting glucose, and seeks to discover and characterize fasting glucose and related trait genetic loci in multi-ethnic population samples (African American, Hispanic, Asian and European). The research will translate new genetic knowledge for clinical and population health benefit using longitudinal and multilevel tests of genetic, social, behavioral, environmental and biophysiological measures of risk for elevated fasting glucose, prediabetes or clinical T2D.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24DK080140-07
Application #
8523836
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2007-09-20
Project End
2017-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
7
Fiscal Year
2013
Total Cost
$185,972
Indirect Cost
$13,776
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Willems, Sara M; Cornes, Belinda K; Brody, Jennifer A et al. (2016) Association of the IGF1 gene with fasting insulin levels. Eur J Hum Genet 24:1337-43
Scott, Robert A; Freitag, Daniel F; Li, Li et al. (2016) A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease. Sci Transl Med 8:341ra76
Teumer, Alexander; Qi, Qibin; Nethander, Maria et al. (2016) Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits. Aging Cell 15:811-24
Raghavan, Sridharan; Pachucki, Mark C; Chang, Yuchiao et al. (2016) Incident Type 2 Diabetes Risk is Influenced by Obesity and Diabetes in Social Contacts: a Social Network Analysis. J Gen Intern Med 31:1127-33
Liu, Gang; Ding, Ming; Chiuve, Stephanie E et al. (2016) Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality Among Men With Type 2 Diabetes: A 22-Year Prospective Study. Arterioscler Thromb Vasc Biol 36:2259-2267
Wang, Shuai; Zhao, Jing Hua; An, Ping et al. (2016) General Framework for Meta-Analysis of Haplotype Association Tests. Genet Epidemiol 40:244-52
Chen, Brian H; Hivert, Marie-France; Peters, Marjolein J et al. (2016) Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations. Diabetes 65:3794-3804
Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa et al. (2016) Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin. Am J Hum Genet 99:56-75
López, Lenny; Grant, Richard W; Marceau, Lisa et al. (2016) Association of Acculturation and Health Literacy with Prevalent Dysglycemia and Diabetes Control Among Latinos in the Boston Area Community Health (BACH) Survey. J Immigr Minor Health 18:1266-1273
Dauriz, Marco; Meigs, James B (2016) The power of numbers. Diabetologia 59:1400-2

Showing the most recent 10 out of 201 publications