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. Laskowitz; Y. 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

doi:10.1038/ki.2015.161

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

Anesthesiology

Research output: Contribution to journal › Article › peer-review

44 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 language	English
Pages (from-to)	823-832
Number of pages	10
Journal	Kidney International
Volume	88
Issue number	4
DOIs	https://doi.org/10.1038/ki.2015.161
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

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10.1038/ki.2015.161

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Stafford-Smith, M., Li, Y. J., Mathew, J. P., Li, Y. W., Ji, Y., Phillips-Bute, B. G., Milano, C. A., Newman, M. F., Kraus, W. E., Kertai, M. D., Shah, S. H., Podgoreanu, M. V., Davis, R. D., Funk, B., Gaca, J. G., Ginsburg, G. S., Glower, D. D., Hall, R. L., Hauser, E., ... White, W. D. (2015). Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci. Kidney International, 88(4), 823-832. https://doi.org/10.1038/ki.2015.161

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

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.",

keywords = "BBS9, GWAS, acute kidney injury, coronary artery bypass graft surgery",

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

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). ",

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doi = "10.1038/ki.2015.161",

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volume = "88",

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Stafford-Smith, M, Li, YJ, Mathew, JP, Li, YW, Ji, Y, Phillips-Bute, BG, Milano, CA, Newman, MF, Kraus, WE, Kertai, MD, Shah, SH, Podgoreanu, MV, Davis, RD, Funk, B, Gaca, JG, Ginsburg, GS, Glower, DD, Hall, RL, Hauser, E, Laskowitz, DT, Li, YJ, Lodge, AJ, Milano, CA, Newman, MF, Phillips-Bute, B, Podgoreanu, MV, Smith, MP, Smith, PK, Swaminathan, M, Welsby, IJ & White, WD 2015, 'Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci', Kidney International, vol. 88, no. 4, pp. 823-832. https://doi.org/10.1038/ki.2015.161

TY - JOUR

T1 - Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci

AU - Stafford-Smith, Mark

AU - Li, Yi Ju

AU - Mathew, Joseph P.

AU - Li, Yen Wei

AU - Ji, Yunqi

AU - Phillips-Bute, Barbara G.

AU - Milano, Carmelo A.

AU - Newman, Mark F.

AU - Kraus, William E.

AU - Kertai, Miklos D.

AU - Shah, Svati H.

AU - Podgoreanu, Mihai V.

AU - Davis, R. D.

AU - Funk, B.

AU - Gaca, J. G.

AU - Ginsburg, G. S.

AU - Glower, D. D.

AU - Hall, R. L.

AU - Hauser, E.

AU - Laskowitz, D. T.

AU - Li, Y. J.

AU - Lodge, A. J.

AU - Milano, C. A.

AU - Newman, M. F.

AU - Phillips-Bute, B.

AU - Podgoreanu, M. V.

AU - Smith, M. P.

AU - Smith, P. K.

AU - Swaminathan, M.

AU - Welsby, I. J.

AU - White, W. D.

N1 - 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).

PY - 2015/10/3

Y1 - 2015/10/3

N2 - 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.

AB - 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.

KW - BBS9

KW - GWAS

KW - acute kidney injury

KW - coronary artery bypass graft surgery

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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