title: Genome-wide assessment for genetic variants associated with ventricular dysfunction after primary coronary artery bypass graft surgery.
abstract: BACKGROUND
  Postoperative ventricular dysfunction (VnD) occurs in 9-20% of coronary artery bypass graft (CABG) surgical patients and is associated with increased postoperative morbidity and mortality. Understanding genetic causes of postoperative VnD should enhance patient risk stratification and improve treatment and prevention strategies. We aimed to determine if genetic variants associate with occurrence of in-hospital VnD after CABG surgery.
  
  
  METHODS
  A genome-wide association study identified single nucleotide polymorphisms (SNPs) associated with postoperative VnD in male subjects of European ancestry undergoing isolated primary CABG surgery with cardiopulmonary bypass. VnD was defined as the need for ≥2 inotropes or mechanical ventricular support after CABG surgery. Validated SNPs were assessed further in two replication CABG cohorts and meta-analysis was performed.
  
  
  RESULTS
  Over 100 SNPs were associated with VnD (P<10(-4)), with one SNP (rs17691914) encoded at 3p22.3 reaching genome-wide significance (P(additive model) = 2.14×10(-8)). Meta-analysis of validation and replication study data for 17 SNPs identified three SNPs associated with increased risk for developing postoperative VnD after adjusting for clinical risk factors. These SNPs are located at 3p22.3 (rs17691914, OR(additive model) = 2.01, P = 0.0002), 3p14.2 (rs17061085, OR(additive model) = 1.70, P = 0.0001) and 11q23.2 (rs12279572, OR(recessive model) = 2.19, P = 0.001).
  
  
  CONCLUSIONS
  No SNPs were consistently associated with strong risk (OR(additive model)>2.1) of developing in-hospital VnD after CABG surgery. However, three genetic loci identified by meta-analysis were more modestly associated with development of postoperative VnD. Studies of larger cohorts to assess these loci as well as to define other genetic mechanisms and related biology that link genetic variants to postoperative ventricular dysfunction are warranted.
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. afox@partners.org
authors: Amanda A
authors: AA
authors: Fox
authors: Mias
authors: M
authors: Pretorius
authors: Kuang-Yu
authors: KY
authors: Liu
authors: Charles D
authors: CD
authors: Collard
authors: Tjorvi E
authors: TE
authors: Perry
authors: Stanton K
authors: SK
authors: Shernan
authors: Philip L
authors: PL
authors: De Jager
authors: David A
authors: DA
authors: Hafler
authors: Daniel S
authors: DS
authors: Herman
authors: Steven R
authors: SR
authors: DePalma
authors: Dan M
authors: DM
authors: Roden
authors: Jochen D
authors: JD
authors: Muehlschlegel
authors: Brian S
authors: BS
authors: Donahue
authors: Dawood
authors: D
authors: Darbar
authors: J G
authors: JG
authors: Seidman
authors: Simon C
authors: SC
authors: Body
authors: Christine E
authors: CE
authors: Seidman
mesh_terms: D000483:Alleles; D015331:Cohort Studies; D001026:Coronary Artery Bypass / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D023281:Genomics; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D018754:Ventricular Dysfunction / Q000235:genetics* / Q000601:surgery; D044465:White People