Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci.
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2015-10
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Abstract
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.
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Stafford-Smith, Mark, Yi-Ju Li, Joseph P Mathew, Yen-Wei Li, Yunqi Ji, Barbara G Phillips-Bute, Carmelo A Milano, Mark F Newman, et al. (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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Scholars@Duke
Mark Stafford-Smith
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.
Yi-Ju Li
My primary research areas include statistical genetics and the genetic investigation of human complex diseases and clinical outcomes. As the group leader of the Biostatistics and Clinical Outcome Group in the Department of Anesthesiology, I also have extensive experience in clinical research, applying both classical statistical modeling and modern machine learning methods to analyze clinical data. Below is a list of my research topics:"
- Statistical genetics: development statistical methods for different genetic data and phenotypic measures
- Genetics of Alzheimer's disease (AD) and age-at-onset (AAO) of AD
- Genetics of Fuchs endothelial corneal dystrophy (FECD)
- Genetic and HLA association for drug induced liver injury (DILI)
- Genetic and clinical research of postoperative outcomes, such as postoperative acute kidney injury, cognitive dysfunction, delirium, etc.
- Biomarker research for osteoarthritis (OA) and its progression
Joseph P. Mathew
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 following cardiopulmonary bypass.
Mark Franklin Newman
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 strategies to improve the outcomes of patients undergoing surgery and anesthesia. Dr. Newman has received funding from the National Institute on Aging, the American Heart Association, the National Heart, Lung and Blood Institute, the Anesthesia Patient Safety Foundation, and the International Anesthesia Research Society to investigate the impact of perioperative outcomes (neurocognitive decline, stroke, myocardial infarction, renal injury) on quantity and quality of life following cardiac surgery and resulting in numerous seminal publications in the New England Journal of Medicine, JAMA and Lancet. Dr. Newman is a popular lecturer and speaker, having appeared on NBC Nightly News and The Today Show and having spoken at more than 200 national and international meetings. Dr. Newman recently stepped down as the Chairman of the Duke University Department after 13 years to assume the role of PDC President. During Dr. Newman’s tenure the department grew exponentially doubling its clinical and academic funding, and developing many outstanding individuals that have gone on to leadership roles at Duke and other key academic institutions across the country.
Svati Hasmukh Shah
Mihai V. Podgoreanu
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 disease.
6. Animal models of vein graft disease.
7. Genetic association studies in perioperative medicine.
8. Clinico-genomic risk prediction models for perioperative and long-term adverse cardiovascular outcomes following cardiac surgery.
Clinical:
9. Intraoperative quantification of tissue perfusion by contrast echocardiography.
10. Use of myocardial tissue deformation indices to characterize perioperative ventricular dysfunction/stunning
11. 3-D echocardiographic evaluation of the right ventricle
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