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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
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Genetic Variants Associated With Atrial Fibrillation and PR Interval Following Cardiac Surgery

Martin I Sigurdsson1, Jochen D Muehlschlegel1, Amanda A Fox2

  • 1Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Journal of Cardiothoracic and Vascular Anesthesia
|May 27, 2015
PubMed

Insights

Patients with postoperative atrial fibrillation (poAF) after coronary artery bypass grafting (CABG) had longer PR intervals. Genetic variants in the 1q21 and 4q25 regions were linked to poAF but not PR interval duration.

Area of Science:

  • Cardiovascular Genetics
  • Cardiac Electrophysiology
  • Surgical Outcomes

Background:

  • Postoperative atrial fibrillation (poAF) is a common complication following coronary artery bypass grafting (CABG).
  • Genetic loci associated with atrial fibrillation (AF) and PR interval have been identified, suggesting potential shared biological pathways.
  • The hypothesis posits that genetic associations are mediated by altered cardiac conduction velocities.

Purpose of the Study:

  • To investigate the association between genetic variants and poAF in patients undergoing CABG.
  • To examine the relationship between these genetic variants and PR interval parameters.
  • To explore whether slower conduction velocities biologically mediate the genetic association between AF and PR interval loci.

Main Methods:

  • Prospective cohort study involving 1227 Caucasian patients undergoing CABG at a single university hospital.
  • Genotyping of 677 single nucleotide polymorphisms (SNPs) previously linked to AF or PR interval.
  • Association analysis of SNPs with poAF, preoperative PR interval, maximum PR interval, and changes in PR interval, with adjustments for false discovery rate (FDR).

Main Results:

  • The incidence of new-onset poAF was 31%.
  • Patients with poAF exhibited significantly longer PR interval variables.
  • Two variants at 1q21 and 12 variants at 4q25 were associated with poAF after FDR adjustment; however, no variants showed significant association with PR interval parameters after FDR adjustment.
  • Several variants showed nominal association (p<0.05) with both poAF and PR interval variables, but none remained significant after FDR correction.

Conclusions:

  • Patients developing poAF after CABG demonstrate significantly prolonged PR intervals.
  • Genetic variants in the 1q21 and 4q25 regions are associated with poAF post-CABG.
  • Despite observed associations with poAF, these genetic variants did not show a significant association with PR interval duration after stringent statistical correction.
Abstract

Keywords:
1q214q25PR intervalatrial fibrillationcardiac surgerygenomics

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