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

Mark Stafford-Smith, Yi Ju Li, Joseph P. Mathew, Yen Wei Li, Yunqi Ji, Barbara G. Phillips-Bute, Carmelo A. Milano, Mark F. Newman, William E. Kraus, Miklos D. Kertai, Svati H. Shah, Mihai V. Podgoreanu, R. D. Davis, B. Funk, J. G. Gaca, G. S. Ginsburg, D. D. Glower, R. L. Hall, E. Hauser, D. T. LaskowitzY. J. Li, A. J. Lodge, C. A. Milano, M. F. Newman, B. Phillips-Bute, M. V. Podgoreanu, M. P. Smith, P. K. Smith, M. Swaminathan, I. J. Welsby, W. D. White

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish
Pages (from-to)823-832
Number of pages10
JournalKidney International
Volume88
Issue number4
DOIs
StatePublished - Oct 3 2015

Bibliographical note

Funding Information:
We thank all patients who participated in this study. This study was funded in part by National Institutes of Health grants HL075273 and HL092071 (to MVP); AG09663, HL054316, and HL069081 (to MFN); HL096978, HL108280, and HL109971 (to JPM); HL095987 (to SHS), and HL101621 (to WEK); American Heart Association grants 0120492U (to MVP), 0256342U (to JPM), and 9970128N (to MFN); and the Duke Clinical Research Centers Program (NIH grant M01-RR-30).

Keywords

  • BBS9
  • GWAS
  • acute kidney injury
  • coronary artery bypass graft surgery

ASJC Scopus subject areas

  • Nephrology

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