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.
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.
|Zhao, Jinying; Zhu, Yun; Lin, Jue et al. (2014) Short leukocyte telomere length predicts risk of diabetes in american indians: the strong heart family study. Diabetes 63:354-62|
|Zhu, Yun; Yang, Jingyun; Li, Shengxu et al. (2014) Genetic variants in nicotinic acetylcholine receptor genes jointly contribute to kidney function in American Indians: the Strong Heart Family Study. J Hypertens 32:1042-8; discussion 1049|
|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|
|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; 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|
|Chen, Shufeng; Lin, Jue; Matsuguchi, Tet et al. (2014) Short leukocyte telomere length predicts incidence and progression of carotid atherosclerosis in American Indians: the Strong Heart Family Study. Aging (Albany NY) 6:414-27|
|Zhu, Yun; Yang, Jingyun; Yeh, Fawn et al. (2014) Joint association of nicotinic acetylcholine receptor variants with abdominal obesity in American Indians: the Strong Heart Family Study. PLoS One 9:e102220|
|Zhu, Yun; Voruganti, V Saroja; Lin, Jue et al. (2013) QTL mapping of leukocyte telomere length in American Indians: the Strong Heart Family Study. Aging (Albany NY) 5:704-16|
|Zhao, Jinying; Goldberg, Jack; Vaccarino, Viola (2013) Leukotriene A4 hydrolase haplotype, diet and atherosclerosis: a twin study. Atherosclerosis 226:238-44|
|Yang, Jingyun; Zhu, Yun; Lee, Elisa T et al. (2013) Joint associations of 61 genetic variants in the nicotinic acetylcholine receptor genes with subclinical atherosclerosis in American Indians: a gene-family analysis. Circ Cardiovasc Genet 6:89-96|
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