title: Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery.
abstract: BACKGROUND
  Atrial fibrillation (AF) is the most common adverse event following coronary artery bypass graft surgery. A recent study identified chromosome 4q25 variants associated with AF in ambulatory populations. However, their role in postoperative AF is unknown. We hypothesized that genetic variants in the 4q25 chromosomal region are independently associated with postoperative AF after coronary artery bypass graft surgery.
  
  
  RESULTS
  Two prospectively collected cohorts of patients undergoing coronary artery bypass graft surgery, with or without concurrent valve surgery, at 3 US centers. From a discovery cohort of 959 patients, clinical and genomic multivariate predictors of postoperative AF were identified by genotyping 45 single-nucleotide polymorphisms (SNPs) encompassing the 4q25 locus. Three SNPs were then assessed in a separately collected validation cohort of 494 patients. After adjustment for clinical predictors of postoperative AF and multiple comparisons, rs2200733, rs13143308, and 5 other linked SNPs independently predicted postoperative AF in the discovery cohort. Additive odds ratios for the 7 associated 4q25 SNPs ranged between 1.57 and 2.17 (P=8.0x10(-4) to 3.4x10(-6)). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort.
  
  
  CONCLUSIONS
  In 2 independently collected cardiac surgery cohorts, noncoding SNPs within the chromosome 4q25 region are independently associated with postoperative AF after coronary artery bypass graft surgery after adjusting for clinical covariates and multiple comparisons.
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115, USA. body@zeus.bwh.harvard.edu
authors.forename: Simon C
authors.initials: SC
authors.lastname: Body
authors.forename: Charles D
authors.initials: CD
authors.lastname: Collard
authors.forename: Stanton K
authors.initials: SK
authors.lastname: Shernan
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Fox
authors.forename: Kuang-Yu
authors.initials: KY
authors.lastname: Liu
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: Tjörvi E
authors.initials: TE
authors.lastname: Perry
authors.forename: Jochen D
authors.initials: JD
authors.lastname: Muehlschlegel
authors.forename: Sary
authors.initials: S
authors.lastname: Aranki
authors.forename: Brian S
authors.initials: BS
authors.lastname: Donahue
authors.forename: Mias
authors.initials: M
authors.lastname: Pretorius
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Estrada
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ellinor
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Christine E
authors.initials: CE
authors.lastname: Seidman
authors.forename: J G
authors.initials: JG
authors.lastname: Seidman
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Herman
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Arne
authors.initials: A
authors.lastname: Pfeufer
authors.forename: Stefan
authors.initials: S
authors.lastname: Kääb
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.forename: Dawood
authors.initials: D
authors.lastname: Darbar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000209:etiology / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000209:etiology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D055815:Young Adult