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

Kidney Int. 2015 Oct;88(4):823-32. doi: 10.1038/ki.2015.161. Epub 2015 Jun 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / genetics*
  • Aged
  • Biomarkers / blood
  • Coronary Artery Bypass / adverse effects*
  • Creatinine / blood
  • Databases, Genetic
  • Female
  • Genetic Loci*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Risk Factors
  • Time Factors

Substances

  • Biomarkers
  • Genetic Markers
  • Creatinine