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.

Methods and 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.

Trial registration: ClinicalTrials.gov NCT00281164.

Conflict of interest statement

Disclosures: None

Figures

Figure 1

Haplotype block structure of the 45 successfully typed 4q25 SNPs in the CABG Genomics discovery cohort. Increasing correlation (r2) between intersecting SNPs is reflected in increasing darker shading within each intersecting square. Correlations and block structure were estimated using HaploView 4.0. Negative log P value of the association of each SNP with postoperative AF for an additive genetic model adjusted for clinical covariates is shown.