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Am J Respir Crit Care Med. 2017 Feb 15;195(4):482-490. doi: 10.1164/rccm.201603-0518OC.

A Genome-Wide Association Study to Identify Single-Nucleotide Polymorphisms for Acute Kidney Injury.

Author information

1
1 Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.
2
2 Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut.
3
3 Program of Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut.
4
4 Program of Applied Translational Research and.
5
5 Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut.
6
6 Clinical Epidemiology Research Center, Veterans Affairs Medical Center, West Haven, Connecticut.
7
7 Division of Nephrology and Hypertension and.
8
8 Vanderbilt Center for Kidney Disease, and.
9
9 Vanderbilt Integrated Program for Acute Kidney Injury Research, Vanderbilt University Medical Center, Nashville, Tennessee.
10
10 Division of Renal Medicine and.
11
11 Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
12
12 Department of Anesthesiology and Pain Management and.
13
13 McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas.
14
14 Department of Anesthesiology, Baylor St. Luke's Medical Center and the Texas Heart Institute, Houston, Texas.
15
15 Lilibeth Caberto Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada.
16
16 Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine.
17
17 Division of Renal Diseases, University of Colorado, Denver, Colorado.
18
18 Division of Nephrology, Department of Medicine and Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
19
19 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; and.
20
20 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut.

Abstract

RATIONALE:

Acute kidney injury is a common and severe complication of critical illness and cardiac surgery. Despite significant attempts at developing treatments, therapeutic advances to attenuate acute kidney injury and expedite recovery have largely failed.

OBJECTIVES:

Identifying genetic loci associated with increased risk of acute kidney injury may reveal novel pathways for therapeutic development.

METHODS:

We conducted an exploratory genome-wide association study to identify single-nucleotide polymorphisms associated with genetic susceptibility to in-hospital acute kidney injury.

MEASUREMENTS AND MAIN RESULTS:

We genotyped 609,508 single-nucleotide polymorphisms and performed genotype imputation in 760 acute kidney injury cases and 669 controls. We then evaluated polymorphisms that showed the strongest association with acute kidney injury in a replication patient population containing 206 cases with 1,406 controls. We observed an association between acute kidney injury and four single-nucleotide polymorphisms at two independent loci on metaanalysis of discovery and replication populations. These include rs62341639 (metaanalysis P = 2.48 × 10-7; odds ratio [OR], 0.64; 95% confidence interval [CI], 0.55-0.76) and rs62341657 (P = 3.26 × 10-7; OR, 0.65; 95% CI, 0.55-0.76) on chromosome 4 near APOL1-regulator IRF2, and rs9617814 (metaanalysis P = 3.81 × 10-6; OR, 0.70; 95% CI, 0.60-0.81) and rs10854554 (P = 6.53 × 10-7; OR, 0.67; 95% CI, 0.57-0.79) on chromosome 22 near acute kidney injury-related gene TBX1.

CONCLUSIONS:

Our findings reveal two genetic loci that are associated with acute kidney injury. Additional studies should be conducted to functionally evaluate these loci and to identify other common genetic variants contributing to acute kidney injury.

KEYWORDS:

cardiac; genetics; genotype; intensive care unit; surgery

PMID:
27576016
PMCID:
PMC5378420
[Available on 2018-02-15]
DOI:
10.1164/rccm.201603-0518OC
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