This mentored research scientist career development award (KOI) proposal is a four-year plan to enable the candidate to develop into an independent investigator in the field of genetic epidemiology for human age-related disorders, in particular cardiovascular disease (CVD). The candidate has been very successful in the area of statistical genetics. However, she lacks formal training in epidemiology, aging biology and clinical cardiology, three crucial components for an outstanding genetic epidemiologist in human chronic disorders. This grant provides a unique opportunity for extensive development of skills in epidemiology, cardiovascular medicine and aging mechanism. These short term career goals will be accomplished through formal course work, extensive mentorship in a collaborative environment, and implementation of a research plan that will form the basis of a larger study aimed at investigating the role of mitochondrial gene polymorphisms in biological aging and CVD. The candidate is currently covered under a Master of Science in Clinical Research (MSCR-KL2) Program which provides her one year didactic training in epidemiological study design, confounding, clinical database management, and chronic disease epidemiology. During the first year of this KOI, she will continue formal training in clinical trials, epidemiological data analysis, grant writing, biology of CVD and aging as well as clinical cardiology. This didactic training will be complemented by the proposed research project, which proposes for the first time that mitochondrial-related genetic variants underlie the biological links among vascular aging, coronary artery disease (CAD) and major adverse cardiac events. This project will take advantage of a large well- characterized patient cohort for coronary angiography (1,000 patients with significant CAD and 1,000 matched controls) that has been compiled and maintained under the direction of her two mentors.
The specific aims are 1) To examine whether mitochondrial-related variants are implicated in biological aging measured by telomere length;and 2) To determine whether mitochondrial-related polymorphisms are associated with CAD and major adverse cardiac events. This K0I award will significantly enhance the candidate's growth and maturation into an independent genetic epidemiologist in human aging disorders, in particular cardiovascular disease.

Public Health Relevance

Coronary artery disease (CAD), a typical aging disorder, is the leading cause of death and disability worldwide. Identification of the link between biological aging and CAD will not only provide novel insights into the pathophysiology of aging and CAD, but may also identify new biomarkers for aging and atherogenesis, which may, ultimately, improve prediction, prevention and treatment of a wide range of age-related disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AG034259-03
Application #
8130921
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Kohanski, Ronald A
Project Start
2009-09-15
Project End
2012-07-02
Budget Start
2011-09-01
Budget End
2012-07-02
Support Year
3
Fiscal Year
2011
Total Cost
$131,237
Indirect Cost
Name
University of Oklahoma Health Sciences Center
Department
Biostatistics & Other Math Sci
Type
Schools of Public Health
DUNS #
878648294
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
Peng, Hao; Yeh, Fawn; de Simone, Giovanni et al. (2017) Relationship between plasma plasminogen activator inhibitor-1 and hypertension in American Indians: findings from the Strong Heart Study. J Hypertens 35:1787-1793
Peng, Hao; Mete, Mihriye; Desale, Sameer et al. (2017) Leukocyte telomere length and ideal cardiovascular health in American Indians: the Strong Heart Family Study. Eur J Epidemiol 32:67-75
Zhao, Qi; Zhu, Yun; Yeh, Fawn et al. (2016) Depressive symptoms are associated with leukocyte telomere length in American Indians: findings from the Strong Heart Family Study. Aging (Albany NY) 8:2961-2970
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Zhao, Jinying; Zhu, Yun; Hyun, Noorie et al. (2015) Novel metabolic markers for the risk of diabetes development in American Indians. Diabetes Care 38:220-7
Zhao, Jinying; An, Qiang; Goldberg, Jack et al. (2015) Promoter methylation of glucocorticoid receptor gene is associated with subclinical atherosclerosis: A monozygotic twin study. Atherosclerosis 242:71-6
Zhang, Mingzhi; An, Qiang; Yeh, Fawn et al. (2015) Smoking-attributable mortality in American Indians: findings from the Strong Heart Study. Eur J Epidemiol 30:553-61
Chen, Shufeng; Yeh, Fawn; Lin, Jue et al. (2014) Short leukocyte telomere length is associated with obesity in American Indians: the Strong Heart Family study. Aging (Albany NY) 6:380-9
Zhao, Jinying; Zhu, Yun; Uppal, Karan et al. (2014) Metabolic profiles of biological aging in American Indians: the Strong Heart Family Study. Aging (Albany NY) 6:176-86
Zhao, Jinying; Roman, Mary J; Devereux, Richard B et al. (2014) Leukotriene haplotype × diet interaction on carotid artery hypertrophy and atherosclerosis in American Indians: the Strong Heart Family Study. Atherosclerosis 233:165-71

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