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 language | English |
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Pages (from-to) | 823-832 |
Number of pages | 10 |
Journal | Kidney International |
Volume | 88 |
Issue number | 4 |
DOIs | |
State | Published - 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