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

• Published in: Kidney international Vol. 88; no. 4; pp. 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: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2015; Elsevier Limited
• 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; coronary artery bypass graft surgery; BBS9; acute kidney injury; GWAS
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.2015.161

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.