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. 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

Anesthesiology

Producción científica: Article › revisión exhaustiva

48 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	823-832
Número de páginas	10
Publicación	Kidney International
Volumen	88
N.º	4
DOI	https://doi.org/10.1038/ki.2015.161
Estado	Published - oct 3 2015

Nota bibliográfica

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).

Financiación

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).

Financiadores	Número del financiador
National Institutes of Health (NIH)	HL069081, HL101621, HL075273, HL095987, HL092071, HL109971, R01HL096978, AG09663, M01-RR-30, R21HL108280
National Heart, Lung, and Blood Institute (NHLBI)	R01HL054316
American the American Heart Association	0256342U, 9970128N, 0120492U

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). ",

year = "2015",

month = oct,

day = "3",

doi = "10.1038/ki.2015.161",

language = "English",

volume = "88",

pages = "823--832",

number = "4",

}

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, n.º 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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UR - https://www.scopus.com/pages/publications/84942988817#tab=citedBy

U2 - 10.1038/ki.2015.161

DO - 10.1038/ki.2015.161

M3 - Article

C2 - 26083657

AN - SCOPUS:84942988817

SN - 0085-2538

VL - 88

SP - 823

EP - 832

JO - Kidney International

JF - Kidney International

IS - 4

ER -

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

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

Acceder al documento

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