Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci.
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Acute kidney injury (AKI) is a common, serious complication of cardiac surgery. Since prior studies have supported a genetic basis for postoperative AKI, we conducted a genome-wide association study (GWAS) for AKI following coronary bypass graft (CABG) surgery. The discovery data set consisted of 873 nonemergent CABG surgery patients with cardiopulmonary bypass (PEGASUS), while a replication data set had 380 cardiac surgical patients (CATHGEN). Single-nucleotide polymorphism (SNP) data were based on Illumina Human610-Quad (PEGASUS) and OMNI1-Quad (CATHGEN) BeadChips. We used linear regression with adjustment for a clinical AKI risk score to test SNP associations with the postoperative peak rise relative to preoperative serum creatinine concentration as a quantitative AKI trait. Nine SNPs meeting significance in the discovery set were detected. The rs13317787 in GRM7|LMCD1-AS1 intergenic region (3p21.6) and rs10262995 in BBS9 (7p14.3) were replicated with significance in the CATHGEN data set and exhibited significantly strong overall association following meta-analysis. Additional fine mapping using imputed SNPs across these two regions and meta-analysis found genome-wide significance at the GRM7|LMCD1-AS1 locus and a significantly strong association at BBS9. Thus, through an unbiased GWAS approach, we found two new loci associated with post-CABG AKI providing new insights into the pathogenesis of perioperative AKI.
SubjectAcute Kidney Injury
Coronary Artery Bypass
Genetic Predisposition to Disease
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Published Version (Please cite this version)10.1038/ki.2015.161
Publication InfoStafford-Smith, Mark; Li, Yi-Ju; Mathew, Joseph P; Li, Yen-Wei; Ji, Yunqi; Phillips-Bute, Barbara G; ... Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team (2015). Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci. Kidney Int, 88(4). pp. 823-832. 10.1038/ki.2015.161. Retrieved from https://hdl.handle.net/10161/13721.
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Associate Professor of Anesthesiology
Richard and Pat Johnson University Distinguished Professor
My training, expertise and research interests range from human integrative physiology and genetics to animal exercise models to cell culture models of skeletal muscle adaptation to mechanical stretch. I am trained clinically as an internist and preventive cardiologist, with particular expertise in preventive cardiology and cardiac rehabilitation. My research training spans molecular biology and cell culture, molecular genetics, and integrative human exercise physiology and metabolism. I pr
Professor of Biostatistics and Bioinformatics
My research interest is in statistical genetics, primarily in statistical method development and its application for genetic research of human complex diseases. Here is the list of research topics: Statistical genetics: I have involved in the development of several family-based association methods for quantitative traits with or without censoring, and for detecting X-linked genes. With the availability of next generation sequencing data, we have ongoing projects to develop
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
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
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
Professor of Medicine
Professor of Anesthesiology
My research interests are in the area of Cardiothoracic Anesthesiology. The main focus of my research is towards the understanding and prevention of acute kidney injury after cardiac and other major surgeries. Secondary interests include the study of analgesic strategies after cardiothoracic surgical procedures, performance of clinical trials, and perioperative transfusion and hemostasis.
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