This application presents a careerdevelopment award proposal connecting the fields of genetic epidemiology, molecular genetics, and cardiovascular medicine. The immediate objective of the current proposal is to developan independent programin patient-oriented researchfocusing on the contribution of genes involved in myocardialinfarction. The ultimate objectiveof the applicant is to translate advances in human genetics into practical benefits for patients with cardiovascular diseases. Support fromthis 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 KansasCity, and merging the dataand DNA samples collected at both sites, the candidate will efficiently maximize his contribution to cardiovascular genetic researchas well as his development as a physician-investigator. With over 1,000 patients clinically characterized, and all of their DNAsamples prepared for genotyping by the applicant, there are substantial preliminary data to support the feasibility of the applicant's proposedproject. 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 andexperiences 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 hiskey role in the design and execution of high-throughput genetic analyses, direct andfrequent interaction with research subjects (the applicant is a clinical geneticist who is also board-certified in family medicine), and application of his formal backgroundin clinical epidemiologyto researchdesign and data analysisin cardiovascular genetics. In addition to providing insight into the clinical importance of knowngenetic variants on myocardial infarction and related outcomes,this projectwill create a repository of ONA and clinical data for future studies designedto discover newgenetic variantsthat may play a role in cardiovascular disease. The experience gained bythe applicant in the conception, design, and performance of this study will serve as a basisfor pursuing his overarching objective of translating genomics into practical clinical knowledge for usein diagnosis andtreatment of patients with cardiovascular diseases.
