Coronary heart disease (CHD) is a leading cause of morbidity and mortality and particularly frequent in type 2 diabetes. Both genetic and environmental factors determine the development of CHD. Recent genome-wide association (GWA) studies have identified several genetic variants for CHD in the general population. It is now a high priority to conduct GWA study for CHD in diabetic patients. In addition, a better understanding of the etiology of CHD requires a careful investigation of intermediate biochemical changes and gene- environment interactions. The Nurses'Health Study (NHS) and Health Professionals'Follow-up Study (HPFS) are well-characterized cohorts whose stored DNA sample and detailed lifestyle information are available. Through a separate NIH grant, we will complete a GWA scan (Affymetrix SNP Array 6.0;~1 million SNPs) in 3,000 diabetic cases (950 CHD/2,050 non-CHD) from NHS/HPFS by July, 2008. We propose to analyze GWA data with the CHD risk and replicate the top 1200-1400 SNPs in two CHD case-control studies of diabetic patients: Joslin Heart Study (N=1,400) and Costa Rica study (N=890). We will also assess the associations with biochemical risk factors for CHD and examine the gene-environment interactions. The GWA scan, biochemical marker measurement, and collection of detailed information on lifestyle factors have been separately granted. Therefore the proposed project will be extremely cost-efficient. We have assembled a solid group of experienced and committed collaborators with expertise in genetic epidemiology, statistical genetics, bioinformatics, cardiovascular disease, diabetes, and nutrition. We believe that the unprecedented resources available in this project will provide a unique opportunity to identify genetic factors for excessive risk of CHD in diabetic patients.

Public Health Relevance

Coronary heart disease (CHD) is 2- to 4-fold higher in patients with type 2 diabetes than the general population. Genome-wide association (GWA) study offers a powerful unbiased method to discover susceptibility genes and provide insights into the etiology of the disease. The overall goal of this project is to conduct GWA analyses (Affymetrix SNP Array 6.0;~1 million SNPs) to identify new genetic variants for the excessive risk of CHD in diabetic patients and to assess the genetic effects on the intermediate biochemical changes, as well as to examine the gene-environment interactions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL071981-08
Application #
8232073
Study Section
Special Emphasis Panel (ZRG1-HOP-T (07))
Program Officer
Sholinsky, Phyliss
Project Start
2003-09-17
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
8
Fiscal Year
2012
Total Cost
$638,411
Indirect Cost
$205,967
Name
Harvard University
Department
Nutrition
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
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