title: Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci.
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.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Stafford-Smith
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA.|Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mathew
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Yen-Wei
authors.initials: YW
authors.lastname: Li
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Phillips-Bute
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Carmelo A
authors.initials: CA
authors.lastname: Milano
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Newman
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina, USA.|Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Miklos D
authors.initials: MD
authors.lastname: Kertai
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina, USA.|Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Mihai V
authors.initials: MV
authors.lastname: Podgoreanu
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D030541:Databases, Genetic; D005260:Female; D056426:Genetic Loci; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D003404:Creatinine