Abstract 4404: Variation in the 4q25 Chromosomal Locus Predicts New-Onset Atrial Fibrillation after Cardiac Surgery

Abstract

Atrial fibrillation (AF) is the most common adverse event following cardiac surgery. A recent genome wide association study identified SNPs associated with AF on chromosome 4q25 adjacent to PITX2, a cardiac transcription factor. However, the role of these genetic variants in post-CABG AF remains unknown. We used clinical and genomic data from 3 major cardiovascular surgical programs to determine the role of 4q25 variants in new-onset postoperative AF. We conducted a prospective observational study of 1,551 consecutive patients undergoing CABG surgery within 3 US centers. Haplotype tagging SNPs encompassing ~300kbp of PITX2 genic region were genotyped. In a discovery cohort of 566 patients, the previously identified SNPs associated with clinical and genomic multivariate predictors of postoperative AF were identified and then assessed in a validation cohort of 985 patients. In the discovery and replication cohorts, 31.4% and 30.0% of patients developed postoperative AF, respectively. A multivariable logistic model of the occurrence of postoperative AF confirmed older age and prior AF to be risk factors for the development of AF. 4q25 SNPs previously associated with ambulatory AF, and other SNPs in linkage disequilibrium described a haplotype that was significantly associated with new-onset postoperative AF. Odds ratio for the associated SNPs ranged between 1.50 and 1.87 (P<10 – 6) in the validation cohort, after accounting for clinical covariates. No SNP within 90kbp of the PITX2 coding region was associated with AF. We have shown in discovery and validation cohorts that non-coding 4q25 SNPs associated with ambulatory AF are also strongly associated with postoperative AF.