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

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 87...

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Bibliographic Details
Published in:Kidney international 2015-10, Vol.88 (4), p.823-832
Main Authors: Stafford-Smith, Mark, Li, Yi-Ju, Mathew, Joseph P., Li, Yen-Wei, Ji, Yunqi, Phillips-Bute, Barbara G., Milano, Carmelo A., Newman, Mark F., Kraus, William E., Kertai, Miklos D., Shah, Svati H., Podgoreanu, Mihai V.
Format: Article
Language:English
Subjects:
acute kidney injury
Acute Kidney Injury - blood
Acute Kidney Injury - diagnosis
Acute Kidney Injury - genetics
Aged
BBS9
Biomarkers - blood
Coronary Artery Bypass - adverse effects
coronary artery bypass graft surgery
Creatinine - blood
Databases, Genetic
Female
Genetic Loci
Genetic Markers
Genetic Predisposition to Disease
Genome-Wide Association Study
GWAS
Humans
Linear Models
Male
Middle Aged
Pegasus
Phenotype
Polymorphism, Single Nucleotide
Risk Assessment
Risk Factors
Time Factors
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Summary: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.
ISSN:0085-2538
1523-1755
DOI:10.1038/ki.2015.161