Genome-wide association study of new-onset atrial fibrillation after coronary artery bypass grafting surgery.

Published

Journal Article

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.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)).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.In patients undergoing CABG surgery, we found genetic polymorphisms in LY96 associated with decreased risk of postoperative AF.

Full Text

Duke Authors

Cited Authors

  • Kertai, MD; Li, Y-J; Ji, Y; Qi, W; Lombard, FW; Shah, SH; Kraus, WE; Stafford-Smith, M; Newman, MF; Milano, CA; Waldron, N; Podgoreanu, MV; Mathew, JP; Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team,

Published Date

  • September 2015

Published In

Volume / Issue

  • 170 / 3

Start / End Page

  • 580 - 90.e28

PubMed ID

  • 26385043

Pubmed Central ID

  • 26385043

Electronic International Standard Serial Number (EISSN)

  • 1097-6744

International Standard Serial Number (ISSN)

  • 0002-8703

Digital Object Identifier (DOI)

  • 10.1016/j.ahj.2015.06.009

Language

  • eng