This application presents a career development award proposal connecting the fields of genetic epidemiology, molecular genetics, and cardiovascular medicine. The immediate objective of the current proposal is to develop an independent program in patient-oriented research focusing on the contribution of genes involved in myocardial infarction. The ultimate objective of the applicant is to translate advances in human genetics into practical benefits for patients with cardiovascular diseases. Support from this grant will facilitate the candidate's efforts to discover genetic influences on the occurrence of and recovery from myocardial infarction among patients in the PREMIERE Registry (Prospective Registry Evaluating outcomes after Myocardial Infarction: Events and Recovery) at Yale-New Haven Hospital. By partnering with the existing PREMIERE research team at Yale-New Haven Hospital and the PREMIERE Study/Acute Coronary Syndrome Registry at Mid-America Heart Institute in Kansas City, and merging the data and DNA samples collected at both sites, the candidate will efficiently maximize his contribution to cardiovascular genetic research as well as his development as a physician-investigator. With over 1,000 patients clinically characterized, and all of their DNA samples prepared for genotyping by the applicant, there are substantial preliminary data to support the feasibility of the applicant's proposed project. This career award will provide vital support for the applicant's efforts to advance knowledge in the field of cardiovascular genetics, building upon his ongoing training in patient-oriented research, molecular genetics, and genetic epidemiology. At the conclusion of the term of this award, the applicant will have gained the skills and experiences needed to develop as a leader in patient-centered genetic analysis of common diseases, with a particular focus on acute coronary syndromes. The educational and research foundations of the applicant's cardiovascular genetics project are his key role in the design and execution of high-throughput genetic analyses, direct and frequent interaction with research subjects (the applicant is a clinical geneticist who is also board-certified in family medicine), and application of his formal background in clinical epidemiology to research design and data analysis in cardiovascular genetics. In addition to providing insight into the clinical importance of known genetic variants on myocardial infarction and related outcomes, this project will create a repository of ONA and clinical data for future studies designed to discover new genetic variants that may play a role in cardiovascular disease. The experience gained by the applicant in the conception, design, and performance of this study will serve as a basis for pursuing his overarching objective of translating genomics into practical clinical knowledge for use in diagnosis and treatment of patients with cardiovascular diseases.
