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

Publication ,  Journal Article
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 ...
Published in: American heart journal
September 2015

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.

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Published In

American heart journal

DOI

EISSN

1097-6744

ISSN

0002-8703

Publication Date

September 2015

Volume

170

Issue

3

Start / End Page

580 / 90.e28

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Odds Ratio
  • Middle Aged
  • Male
  • Lymphocyte Antigen 96
  • Incidence
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
 

Citation

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Kertai, M. D., Li, Y.-J., Ji, Y., Qi, W., Lombard, F. W., Shah, S. H., … Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team, . (2015). Genome-wide association study of new-onset atrial fibrillation after coronary artery bypass grafting surgery. American Heart Journal, 170(3), 580-90.e28. https://doi.org/10.1016/j.ahj.2015.06.009
Kertai, Miklos D., Yi-Ju Li, Yunqi Ji, Wenjing Qi, Frederick W. Lombard, Svati H. Shah, William E. Kraus, et al. “Genome-wide association study of new-onset atrial fibrillation after coronary artery bypass grafting surgery.American Heart Journal 170, no. 3 (September 2015): 580-90.e28. https://doi.org/10.1016/j.ahj.2015.06.009.
Kertai MD, Li Y-J, Ji Y, Qi W, Lombard FW, Shah SH, et al. Genome-wide association study of new-onset atrial fibrillation after coronary artery bypass grafting surgery. American heart journal. 2015 Sep;170(3):580-90.e28.
Kertai, Miklos D., et al. “Genome-wide association study of new-onset atrial fibrillation after coronary artery bypass grafting surgery.American Heart Journal, vol. 170, no. 3, Sept. 2015, pp. 580-90.e28. Epmc, doi:10.1016/j.ahj.2015.06.009.
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. Genome-wide association study of new-onset atrial fibrillation after coronary artery bypass grafting surgery. American heart journal. 2015 Sep;170(3):580–90.e28.
Journal cover image

Published In

American heart journal

DOI

EISSN

1097-6744

ISSN

0002-8703

Publication Date

September 2015

Volume

170

Issue

3

Start / End Page

580 / 90.e28

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Odds Ratio
  • Middle Aged
  • Male
  • Lymphocyte Antigen 96
  • Incidence
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease