Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci.

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Stafford-Smith, Mark

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Li, Yi-Ju

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Mathew, Joseph P

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Li, Yen-Wei

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Ji, Yunqi

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Phillips-Bute, Barbara G

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Milano, Carmelo A

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Newman, Mark F

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Kraus, William E

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Kertai, Miklos D

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Shah, Svati H

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Podgoreanu, Mihai V

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Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team

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United States

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2017-03-01T14:57:06Z

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2017-03-01T14:57:06Z

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2015-10

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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.

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http://www.ncbi.nlm.nih.gov/pubmed/26083657

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S2157-1716(15)32247-4

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1523-1755

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https://hdl.handle.net/10161/13721

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eng

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Elsevier BV

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Kidney Int

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10.1038/ki.2015.161

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Acute Kidney Injury

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Aged

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Biomarkers

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Coronary Artery Bypass

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Creatinine

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Databases, Genetic

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Female

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Genetic Loci

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Genetic Markers

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Genetic Predisposition to Disease

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Genome-Wide Association Study

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Humans

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Linear Models

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Male

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Middle Aged

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Phenotype

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Polymorphism, Single Nucleotide

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Risk Assessment

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Risk Factors

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Time Factors

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Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci.

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Journal article

duke.contributor.orcid

Li, Yi-Ju|0000-0001-6996-4834

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Mathew, Joseph P|0000-0002-3815-4131

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Kraus, William E|0000-0003-1930-9684

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Shah, Svati H|0000-0002-3495-2830

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/26083657

pubs.begin-page

823

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832

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4

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Anesthesiology

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Anesthesiology, Cardiothoracic

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Basic Science Departments

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Biomedical Engineering

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Biostatistics & Bioinformatics

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Clinical Science Departments

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Duke

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Duke Cancer Institute

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Duke Clinical Research Institute

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Duke Molecular Physiology Institute

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Institutes and Centers

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Medicine

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Medicine, Cardiology

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Pathology

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Pediatrics

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Pratt School of Engineering

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School of Medicine

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School of Nursing

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School of Nursing - Secondary Group

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Surgery

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Surgery, Cardiovascular and Thoracic Surgery

pubs.publication-status

Published

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88

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