The overarching long range goal of this program project is to carry out translational research leading to the identification of genetic variants that act to increase the expression of endophenotypes that lead over time to the development of CVD and Type 2 diabetes (T2D), a major CVD risk factor. The central organizing theme of our research toward this goal over the next five years posits that genes and environmental exposures to various acute and chronic stressors across the life cycle influence - via both main and interactive effects -brain neurotransmitter systems in ways that affect the expression of health behaviors, psychological traits and states and neuroendocrine/autonomic functions in ways that alter metabolic, hemostatic, inflammatory and cardiovascular functions that are the proximal contributors to the development of T2D and/or CVD and/or precipitation of acute clinical events. Project 1 will use three existing samples with extensive data on these CVD and T2D endophenotypes to identify promising gene variants - using both candidate genes and GWAS-derived SNPs associated with T2D and CVD ~ that can be evaluated in Projects 2 and 3 for association with the same or similar predisease endophenotypes and CVD and/or T2D prevalence/incidence in two large cohorts. Project 2 will attempt to replicate the gene associations with the same or similar T2D and/or CVD endophenotypes found in Project 1 and test those variants for association with CVD and T2D in a large healthy nationally representative cohort, the Add Health sample (N=15,608). Project 3 will test these genetic variants for association with CVD &T2D and clinical events in a large cohort (N =8,000 -10,000) of Duke CAD patients who have undergone coronary angiography.

Public Health Relevance

The knowledge gained can be used to guide the development of the new field of prospective medicine, in which individuals at high risk of developing CVD and/or T2D can be identified earlier in the pathogenic process - before tissue damage has occurred - and targeted for preventive interventions to slow or prevent the development of disease and/or improve prognosis once disease is present.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL036587-24
Application #
8644123
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Czajkowski, Susan
Project Start
1993-08-20
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
24
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Duke University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Durham
State
NC
Country
United States
Zip Code
27705
Williams, Redford B; Bishop, George D; Haberstick, Brett C et al. (2017) Population differences in associations of serotonin transporter promoter polymorphism (5HTTLPR) di- and triallelic genotypes with blood pressure and hypertension prevalence. Am Heart J 185:110-122
Jiang, Rong; Babyak, Michael A; Brummett, Beverly H et al. (2017) Brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism is associated with disease severity and incidence of cardiovascular events in a patient cohort. Am Heart J 190:40-45
Jiang, Rong; Babyak, Michael A; Brummett, Beverly H et al. (2017) Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism interacts with gender to influence cortisol responses to mental stress. Psychoneuroendocrinology 79:13-19
Haberstick, Brett C; Boardman, Jason D; Wagner, Brandon et al. (2016) Depression, Stressful Life Events, and the Impact of Variation in the Serotonin Transporter: Findings from the National Longitudinal Study of Adolescent to Adult Health (Add Health). PLoS One 11:e0148373
McGarrah, Robert W; Craig, Damian M; Haynes, Carol et al. (2016) High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort. Atherosclerosis 246:229-35
Ward-Caviness, Cavin K; Neas, Lucas M; Blach, Colette et al. (2016) Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease. PLoS One 11:e0152670
Ogle, Christin M; Rubin, David C; Siegler, Ilene C (2016) Accounting for Posttraumatic Stress Disorder Symptom Severity With Pre- and Posttrauma Measures: A Longitudinal Study of Older Adults. Clin Psychol Sci 4:272-286
Davey, Adam; Siegler, Ilene C; Martin, Peter et al. (2015) Personality Structure Among Centenarians: The Georgia Centenarian Study. Exp Aging Res 41:361-85
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
Ogle, Christin M; Rubin, David C; Siegler, Ilene C (2015) The relation between insecure attachment and posttraumatic stress: Early life versus adulthood traumas. Psychol Trauma 7:324-32

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