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

dc.contributor.author Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team
dc.contributor.author Ji, Y
dc.contributor.author Kertai, Miklos David
dc.contributor.author Kraus, William Erle
dc.contributor.author Li, YJ
dc.contributor.author Li, YW
dc.contributor.author Mathew, Joseph P
dc.contributor.author Milano, Carmelo Alessio
dc.contributor.author Newman, Mark Franklin
dc.contributor.author Phillips-Bute, Barbara Gottfried
dc.contributor.author Podgoreanu, Mihai V
dc.contributor.author Shah, SH
dc.contributor.author Stafford-Smith, Mark
dc.coverage.spatial United States
dc.date.accessioned 2017-03-01T14:57:06Z
dc.date.available 2017-03-01T14:57:06Z
dc.date.issued 2015-10
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/26083657
dc.identifier S2157-1716(15)32247-4
dc.identifier.uri https://hdl.handle.net/10161/13721
dc.description.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.
dc.language eng
dc.relation.ispartof Kidney Int
dc.relation.isversionof 10.1038/ki.2015.161
dc.subject Acute Kidney Injury
dc.subject Aged
dc.subject Biomarkers
dc.subject Coronary Artery Bypass
dc.subject Creatinine
dc.subject Databases, Genetic
dc.subject Female
dc.subject Genetic Loci
dc.subject Genetic Markers
dc.subject Genetic Predisposition to Disease
dc.subject Genome-Wide Association Study
dc.subject Humans
dc.subject Linear Models
dc.subject Male
dc.subject Middle Aged
dc.subject Phenotype
dc.subject Polymorphism, Single Nucleotide
dc.subject Risk Assessment
dc.subject Risk Factors
dc.subject Time Factors
dc.title Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/26083657
pubs.begin-page 823
pubs.end-page 832
pubs.issue 4
pubs.organisational-group Anesthesiology
pubs.organisational-group Anesthesiology, Cardiothoracic
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biomedical Engineering
pubs.organisational-group Biostatistics & Bioinformatics
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Duke Molecular Physiology Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Pathology
pubs.organisational-group Pediatrics
pubs.organisational-group Pratt School of Engineering
pubs.organisational-group School of Medicine
pubs.organisational-group School of Nursing
pubs.organisational-group School of Nursing - Secondary Group
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Cardiovascular and Thoracic Surgery
pubs.publication-status Published
pubs.volume 88
dc.identifier.eissn 1523-1755


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