title: A Genome-Wide Association Study to Identify Single-Nucleotide Polymorphisms for Acute Kidney Injury.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors: 1 Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.
authors: Bixiao
authors: B
authors: Zhao
authors: 2 Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut.
authors: Qiongshi
authors: Q
authors: Lu
authors: 3 Program of Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut.
authors: Yuwei
authors: Y
authors: Cheng
authors: 4 Program of Applied Translational Research and.|5 Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut.|6 Clinical Epidemiology Research Center, Veterans Affairs Medical Center, West Haven, Connecticut.
authors: Justin M
authors: JM
authors: Belcher
authors: 7 Division of Nephrology and Hypertension and.|8 Vanderbilt Center for Kidney Disease, and.|9 Vanderbilt Integrated Program for Acute Kidney Injury Research, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Edward D
authors: ED
authors: Siew
authors: 10 Division of Renal Medicine and.
authors: David E
authors: DE
authors: Leaf
authors: 11 Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Simon C
authors: SC
authors: Body
authors: 12 Department of Anesthesiology and Pain Management and.|13 McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas.
authors: Amanda A
authors: AA
authors: Fox
authors: 10 Division of Renal Medicine and.
authors: Sushrut S
authors: SS
authors: Waikar
authors: 14 Department of Anesthesiology, Baylor St. Luke's Medical Center and the Texas Heart Institute, Houston, Texas.
authors: Charles D
authors: CD
authors: Collard
authors: 4 Program of Applied Translational Research and.|5 Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut.|15 Lilibeth Caberto Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada.
authors: Heather
authors: H
authors: Thiessen-Philbrook
authors: 7 Division of Nephrology and Hypertension and.|8 Vanderbilt Center for Kidney Disease, and.|9 Vanderbilt Integrated Program for Acute Kidney Injury Research, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: T Alp
authors: TA
authors: Ikizler
authors: 16 Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine.
authors: Lorraine B
authors: LB
authors: Ware
authors: 17 Division of Renal Diseases, University of Colorado, Denver, Colorado.
authors: Charles L
authors: CL
authors: Edelstein
authors: 15 Lilibeth Caberto Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada.|18 Division of Nephrology, Department of Medicine and Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.|19 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; and.
authors: Amit X
authors: AX
authors: Garg
authors: 1 Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.
authors: Murim
authors: M
authors: Choi
authors: 4 Program of Applied Translational Research and.
authors: Jennifer A
authors: JA
authors: Schaub
authors: 1 Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.|2 Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut.
authors: Hongyu
authors: H
authors: Zhao
authors: 1 Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.|20 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut.
authors: Richard P
authors: RP
authors: Lifton
authors: 4 Program of Applied Translational Research and.|5 Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut.|6 Clinical Epidemiology Research Center, Veterans Affairs Medical Center, West Haven, Connecticut.
authors: Chirag R
authors: http://orcid.org/0000-0001-9051-7385
authors: CR
authors: Parikh
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics*; D000328:Adult; D000368:Aged; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D016022:Case-Control Studies; D016638:Critical Illness; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D050836:Interferon Regulatory Factor-2 / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000235:genetics*; D012307:Risk Factors; D018709:Statistics, Nonparametric; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D015415:Biomarkers; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; D008075:Lipoproteins, HDL; D020825:T-Box Domain Proteins; C108625:TBX1 protein, human
keywords: cardiac; genetics; genotype; intensive care unit; surgery