title: Genome-wide association study of new-onset atrial fibrillation after coronary artery bypass grafting surgery.
abstract: BACKGROUND
  Postoperative atrial fibrillation (AF) is a potentially life-threatening complication after coronary artery bypass graft (CABG) surgery. Genetic predisposition may predict risk for developing postoperative AF.
  
  
  METHODS
  Study subjects underwent CABG surgery with cardiopulmonary bypass at Duke University Medical Center. In a discovery cohort of 877 individuals from the Perioperative Genetics and Safety Outcomes Study, we performed a genome-wide association study using a logistic regression model with a covariate adjustment for AF risk index. Single-nucleotide polymorphisms (SNPs) that met a P < 5 × 10(-5) were further tested using a replication dataset of 304 individuals from the CATHeterization GENetics biorepository, followed by meta-analysis. Potential pathways related to postoperative AF were identified through gene enrichment analysis using the top genome-wide association study SNPs (P < 10(-4)).
  
  
  RESULTS
  Nineteen SNPs met the a priori defined discovery threshold for replication, but only 3 met nominal significance (P < .05) in the CATHeterization GENetics group, with only one-rs10504554, in the intronic region in lymphocyte antigen 96 (LY96)-showing the same direction of the effect for postoperative AF (odds ratio [OR] 0.48, 95% CI 0.34-0.68, P = 2.9 × 10(-5) vs OR 0.55, 95% CI 0.31-0.99, P = .046) and strong overall association by meta-analysis (meta-P = 4.0 × 10(-6)). Gene enrichment analysis highlighted the role of LY96 in pathways of biologic relevance to activation and modulation of innate immune responses. Our analysis also showed potential association between LY96 and nuclear factor κ-B interaction and postoperative AF through their relevance to inflammatory signaling pathways.
  
  
  CONCLUSIONS
  In patients undergoing CABG surgery, we found genetic polymorphisms in LY96 associated with decreased risk of postoperative AF.
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC. Electronic address: miklos.kertai@duke.edu.
authors.forename: Miklos D
authors.initials: MD
authors.lastname: Kertai
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC; Molecular Physiology Institute, Duke University Medical Center, Durham, NC.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC.
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Qi
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC.
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Lombard
authors.affiliation: Molecular Physiology Institute, Duke University Medical Center, Durham, NC; Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
authors.affiliation: Molecular Physiology Institute, Duke University Medical Center, Durham, NC; Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC.
authors.forename: Mark
authors.initials: M
authors.lastname: Stafford-Smith
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Newman
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC.
authors.forename: Carmelo A
authors.initials: CA
authors.lastname: Milano
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC.
authors.forename: Nathan
authors.initials: N
authors.lastname: Waldron
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC.
authors.forename: Mihai V
authors.initials: MV
authors.lastname: Podgoreanu
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mathew
mesh_terms: D001281:Atrial Fibrillation / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003324:Coronary Artery Disease / Q000150:complications / Q000601:surgery*; D004247:DNA / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015994:Incidence; D051218:Lymphocyte Antigen 96 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
chemical_list: C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; D004247:DNA