The overarching objective of this Project is to identify genetic variants and environmental factors that act, whether interactively or Independently (main effects), to influence the expression of a wide range of psychosocial, behavioral and biological characteristics [CVD and Type 2 Diabetes (T2D) endophenotypes] that increase the risk of developing CVD and T2D among healthy persons as well as increase the risk of adverse clinical events in persons in whom CVD is already manifest. To achieve this objective we shall use use three samples - PPG-1 (N=165), Caregiver (170 caregivers of a relative with Alzheimer's Disease, 170 controls) and PPG-2 (644 from 400 families);with a total N of 1000+/- - in which we have extensive data re a broad range of T2D and CVD endophenotypes to identify promising genetic variants (using both candidate genes and GWAS-derived SNPs) that are associated with these predisease endophenotypes. A major thrust of our work on this Project will be to increase our confidence in the reality of these geneendophenotype associations by replicating them, both within the three samples used by Project 1 and in the large healthy and clinical CAD samples being studied in Projects 2 and 3.
A third aim will be to work closely with Projects 2 and 3 to complete the tranlational process, by showing that the genetic variants found associated in Project 1 with T2D and CVD endophenotypes are also associated in those Projects'samples with both the prevalence and incidence of CVD and T2D and clinical course.

Public Health Relevance

The knowledge gained in Project 1 and its collaboration with Projects 2 and 3 will consitute important progress toward the long range goal identifying persons at risk of developing CVD or T2D earlier in the pathogenic process, so that they, and the CVD and/or T2D endophenotype(s) accounting for their increased risk, can be targeted for interventions, to prevent the development of disease or improve prognosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL036587-22
Application #
8378679
Study Section
Special Emphasis Panel (ZHL1-PPG-Z)
Project Start
Project End
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
22
Fiscal Year
2012
Total Cost
$589,097
Indirect Cost
$70,166
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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Singh, Abanish; Babyak, Michael A; Brummett, Beverly H et al. (2015) Computing a Synthetic Chronic Psychosocial Stress Measurement in Multiple Datasets and its Application in the Replication of G × E Interactions of the EBF1 Gene. Genet Epidemiol 39:489-97
Boyle, Stephen H; Georgiades, Anastasia; Brummett, Beverly H et al. (2015) Associations between central nervous system serotonin, fasting glucose, and hostility in African American females. Ann Behav Med 49:49-57
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