Survival and Age Biases in Gene Associations with Coronary Disease

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DESCRIPTION (provided by applicant): This is a resubmission for a NIH Pathway to Independence Career Development Award (# 1K99 NR011054- 01). The candidate for this award is Jennifer R. Dungan, PhD, RN, a Senior Research Associate at the Duke University School of Nursing and Duke Center for Aging/John A. Hartford Junior Faculty Fellow. Drs. William E. Kraus, Elizabeth R. Hauser, Svati H. Shah, and Catherine L. Gilliss will serve as co-mentors during the mentored phase of this award. The overarching goal of this proposal is for the candidate to build a research program in the genetics of survivorship in coronary artery disease, a research program that combines her interests in aging, cardiovascular disease, and genetics. Dr. Dungan has established the phenotype for survivorship in coronary artery disease in two existing databases (the Duke CATHeterization GENetics [CATHGEN] and the Framingham Heart studies) and has performed pilot analysis to identify survival and age biases in these datasets. In order to effectively study the genetics of survivorship in coronary artery disease, it is necessary to first understand the impact of survival and age biases on gene associations with coronary artery disease and control for their effects. Her proposed mentored research seeks to extensively characterize these biases in both datasets, then test traditional and complex statistical methods to control for such biases in gene associations with coronary artery disease. The independent phase research seeks to identify other epidemiological datasets to further characterize the scope of such biases and test the statistical methods from the mentored phase. Results from these aims will inform the proper development of a pilot study of a prospective, epidemiological investigation of the genetics of survivorship in coronary artery disease (final independent phase aim). Dr. Dungan's training plan includes strengthening her background in genetic epidemiology, statistical genetics, and statistical handling of time-related effects. Given the candidate's strong background in genetics and her experience with research projects in cardiovascular aging and genomics, a strong epidemiological and statistical knowledge base will enhance her future productivity and potential in this competitive field. The goal is that from this research, heart disease patients may be better screened and identified for genetic risk and/or protective genes, potentially leading to prevention of heart-disease-related events and promotion of healthy survival. PUBLIC HEALTH RELEVANCE: Many genes have been identified for heart disease. The impact of genetic variation may vary by age and our ability to detect these effects may be impacted by who survives to be in the study. If there are genes specifically related to surviving with heart disease, they may be important to understanding risk for heart attacks and death and can also provide information about genetic protection against these risks. This research may help improve health outcomes and survival for people with heart disease.