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Project Director: Aravinda Chakravarti, Ph.D.
Co Investigators: Dan E. Arking, Ph.D., Peter Spooner, Ph.D., Sumeet Chugh, M.D., Wendy Post, M.D.
The central goal of this project is to develop and apply new whole-genome genetic technologies that take advantage of the recently defined human genome sequence to identify new coding and regulatory genetic sequences that enhance susceptibility to sudden cardiac death (SCD). Studies will be performed on DNA from a number of cohorts, including those individuals with atherosclerotic disease who succumb in the Oregon-Sudden Unexpected Death Study (Or-SUDS) directed by collaborator Sumeet Chugh, a number of the larger NIH funded epidemiological studies and other national activities under the supervision of collaborator Greg Burke, (External Project 3) at Wake Forest University. Genomic determinants are likely to be associated with an increased incidence of arrhythmias in some patients who have been instrumented with an implantable cardioverter defibrillator (ICD). Therefore, candidate gene sources of susceptibility will be examined in a well-defined high-risk ICD population being established in the Registry in Project 3. Samples will be drawn from patients who have frequent firings during follow-up and compared to those who have no firings. The goal is to examine the genetic underpinnings of increased ICD firings, a surrogate for SCD events. Candidate gene approaches performed with the assistance of Mark Keating (External Project 2), as well as whole genome association (WGA) and other genetic approaches developed in our laboratories, will be applied to elucidate those inherited influences which enhance SCD risk specifically in those patients who succumb to coronary artery disease.
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