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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Stafford-Smith, M; Li, Y-J; Mathew, JP; Li, Y-W; Ji, Y; Phillips-Bute, BG; Milano, CA; Newman, MF; Kraus, WE; Kertai, MD; Shah, SH; Podgoreanu, MV; Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team,

Published Date

  • October 2015

Published In

Volume / Issue

  • 88 / 4

Start / End Page

  • 823 - 832

PubMed ID

  • 26083657

Pubmed Central ID

  • 26083657

Electronic International Standard Serial Number (EISSN)

  • 1523-1755

Digital Object Identifier (DOI)

  • 10.1038/ki.2015.161

Language

  • eng

Conference Location

  • United States