Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery.
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OBJECTIVES: Identification of patient subpopulations susceptible to develop myocardial infarction (MI) or, conversely, those displaying either intrinsic cardioprotective phenotypes or highly responsive to protective interventions remain high-priority knowledge gaps. We sought to identify novel common genetic variants associated with perioperative MI in patients undergoing coronary artery bypass grafting using genome-wide association methodology. SETTING: 107 secondary and tertiary cardiac surgery centres across the USA. PARTICIPANTS: We conducted a stage I genome-wide association study (GWAS) in 1433 ethnically diverse patients of both genders (112 cases/1321 controls) from the Genetics of Myocardial Adverse Outcomes and Graft Failure (GeneMAGIC) study, and a stage II analysis in an expanded population of 2055 patients (225 cases/1830 controls) combined from the GeneMAGIC and Duke Perioperative Genetics and Safety Outcomes (PEGASUS) studies. Patients undergoing primary non-emergent coronary bypass grafting were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome variable was perioperative MI, defined as creatine kinase MB isoenzyme (CK-MB) values ≥10× upper limit of normal during the first postoperative day, and not attributable to preoperative MI. Secondary outcomes included postoperative CK-MB as a quantitative trait, or a dichotomised phenotype based on extreme quartiles of the CK-MB distribution. RESULTS: Following quality control and adjustment for clinical covariates, we identified 521 single nucleotide polymorphisms in the stage I GWAS analysis. Among these, 8 common variants in 3 genes or intergenic regions met p<10(-5) in stage II. A secondary analysis using CK-MB as a quantitative trait (minimum p=1.26×10(-3) for rs609418), or a dichotomised phenotype based on extreme CK-MB values (minimum p=7.72×10(-6) for rs4834703) supported these findings. Pathway analysis revealed that genes harbouring top-scoring variants cluster in pathways of biological relevance to extracellular matrix remodelling, endoplasmic reticulum-to-Golgi transport and inflammation. CONCLUSIONS: Using a two-stage GWAS and pathway analysis, we identified and prioritised several potential susceptibility loci for perioperative MI.
Coronary Artery Bypass
Genome-Wide Association Study
Published Version (Please cite this version)10.1136/bmjopen-2014-006920
Publication InfoKertai, Miklos D; Li, Yi-Ju; Li, Yen-Wei; Ji, Yunqi; Alexander, John; Newman, Mark F; ... Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team (2015). Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery. BMJ Open, 5(5). pp. e006920. 10.1136/bmjopen-2014-006920. Retrieved from https://hdl.handle.net/10161/11099.
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John Hunter Peel Alexander
Professor of Medicine
John H. Alexander, MD, MHS is a cardiologist and Professor of Medicine in the Department of Medicine, Division of Cardiology at Duke University School of Medicine, as well as the Vice Chief, Clinical Research in the Division of Cardiology. He is the Director of Cardiovascular Research at the Duke Clinical Research Institute where he oversees a large group of clinical research faculty and a broad portfolio of cardiovascular clinical trials and observational clinical research programs. He is a
Miklos David Kertai
Associate Professor of Anesthesiology
Professor of Biostatistics & Bioinformatics
My research interest is in statistical genetics, including statistical method development and its application for understanding the genetic predisposition of human complex diseases. Here is the list of research topics: Statistical genetics: development of family-based association methods for quantitative traits with or without censoring and for detecting X-linked genes for disease risk. With the availability of next generation sequencing data, we have ongoing projects to d
Joseph P. Mathew
Jerry Reves, M.D. Distinguished Professor of Cardiac Anesthesiology
Current research interests include:1. The relationship between white matter patency, functional connectivity (fMRI) and neurocognitive function following cardiac surgery.2. The relationship between global and regional cortical beta-amyloid deposition and postoperative cognitive decline.3. The effect of lidocaine infusion upon neurocognitive function following cardiac surgery.4. The association between genotype and outcome after cardiac surgery.5. Atrial fibrillation
Mark Franklin Newman
Merel H. Harmel Distinguished Professor Emeritus of Anesthesiology
Best known for his work in assessing and improving clinical outcomes and quality of life following cardiac surgery, Dr. Mark Newman is President of the Duke Private Diagnostic Clinic (The Duke Faculty Practice Organization) and the Merel H. Harmel Professor of Anesthesiology at Duke University Medical Center. In addition, Dr. Newman developed the Multicenter Perioperative Outcomes Research Group of the Duke Clinical Research Institute established at Duke in 2001 to further the study of strategie
Mihai V. Podgoreanu
Associate Professor of Anesthesiology
Basic-Translational: 1. Systems biology approaches to modeling perioperative cardiovascular injury and adaptation. 2. Mechanisms of perioperative myocardial injury; functional genomics applied to perioperative myocardial injury. 3. Metabolic consequences of perioperative myocardial ischemia-reperfusion injury. 4. Animal models and comparative genomic approaches to study perioperative myocardial ischemia-reperfusion injury. 5. Functional genomics of vein graft diseas
Peter Kent Smith
Mary and Deryl Hart Distinguished Professor of Surgery, in the School of Medicine
Dr. Smith is the Prinicpal Investigator for the Duke site in the Cardiothoracic Surgery Clinical Trials Network (CTSN) and in recent years has focused his research efforts in clinical research. The CTSN is an NHLBI sponsored network developed to promote clinical research in cardiac surgery, and is now entering its 7th year of funding with a commitment now for an additional 5 years. Dr. Smith is the national PI for a randomized clinical trial comparing CABG alone to CABG with mitral repair f
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