The overarching objective of this Project is to identify genetic variants that are associated, both as main effects and via interactions with exposure to environmental stressors, with incident cardiovascular events or coronary artery disease (CAD). To accomplish this goal, we will evaluate genes found associated in Projects 1 and 2 with CVD endophenotypes or in Project 3 with hypertension or type II diabetes (T2D), for associations with incident cardiovascular events and angiographically documented CAD in the CATHGEN sample of approximately 10,000 patients who have undergone cardiac catheterization at Duke since 2001. CATHGEN is a unique resource of biological samples collected at time of cardiac catheterization combined with a carefully adjudicated clinical database comprising angiographically-defined extent and anatomical distribution of coronary artery disease, extensive clinical data on CHD risk factors, and annual follow-up for evaluation of incident cardiovascular events. The CATHGEN investigators, under non-overlapping support from their NHLBI grant, will be evaluating a broad range of genes that are biologically plausible contributors to CHD pathogenesis and/or course or have been reported to be associated with CHD for associations with CAD and clinical events. Therefore, another aim of this Project, will be to collaborate with Projects 1, 2 and 3 to determine whether any genetic variants we fmd associated with CAD or clinical events in the CATHGEN sample are also associated with CVD endophenotypes, hypertension and/or T2D in their samples. As with Project 3, this Project provides the opportunity to take the critical step of translating gene associations with CVD endophenotypes into documented impact on disease endpoints.

Public Health Relevance

The knowledge gained can be used to identify persons at risk who can be selected for behavioral and/or pharmacologic interventions that target the CVD endophenotypes via which gene effects on pathogenesis or disease course are mediated, with the goals or preventing disease and improving 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 #
5P01HL036587-23
Application #
8445379
Study Section
Special Emphasis Panel (ZHL1-PPG-Z)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
23
Fiscal Year
2013
Total Cost
$502,519
Indirect Cost
$181,923
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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Brummett, Beverly H; Babyak, Michael A; Kuhn, Cynthia M et al. (2014) A functional polymorphism in the HTR2C gene associated with stress responses: a validation study. Biol Psychol 103:317-21
Ogle, Christin M; Rubin, David C; Siegler, Ilene C (2014) Changes in neuroticism following trauma exposure. J Pers 82:93-102
Siegler, Ilene C; Brummett, Beverly H; Martin, Peter et al. (2013) Consistency and timing of marital transitions and survival during midlife: the role of personality and health risk behaviors. Ann Behav Med 45:338-47
Berger, Jeffrey S; Becker, Richard C; Kuhn, Cynthia et al. (2013) Hyperreactive platelet phenotypes: relationship to altered serotonin transporter number, transport kinetics and intrinsic response to adrenergic co-stimulation. Thromb Haemost 109:85-92
Jiang, Rong; Brummett, Beverly H; Babyak, Michael A et al. (2013) Brain-derived neurotrophic factor (BDNF) Val66Met and adulthood chronic stress interact to affect depressive symptoms. J Psychiatr Res 47:233-9
Jiang, Rong; Brummett, Beverly H; Hauser, Elizabeth R et al. (2013) Chronic family stress moderates the association between a TOMM40 variant and triglyceride levels in two independent Caucasian samples. Biol Psychol 93:184-9
Ogle, Christin M; Rubin, David C; Siegler, Ilene C (2013) The impact of the developmental timing of trauma exposure on PTSD symptoms and psychosocial functioning among older adults. Dev Psychol 49:2191-200
Brummett, Beverly H; Babyak, Michael A; Singh, Abanish et al. (2013) Socioeconomic indices as independent correlates of C-reactive protein in the National Longitudinal Study of Adolescent Health. Psychosom Med 75:882-93
Nolan, Daniel; Kraus, William E; Hauser, Elizabeth et al. (2013) Genome-wide linkage analysis of cardiovascular disease biomarkers in a large, multigenerational family. PLoS One 8:e71779

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