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

Abstract

BACKGROUND 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. METHODS 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 (PEGASUS), we performed a genome-wide association study (GWAS) 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 (CATHGEN) biorepository, followed by meta-analysis. Potential pathways related to postoperative AF were identified through gene enrichment analysis using the top GWAS SNPs (P<10−4). RESULTS Nineteen SNPs met the a priori defined discovery threshold for replication, but only 3 met nominal significance (P<0.05) in the CATHGEN 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=0.046), 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 NF-kappa-B interaction, and postoperative AF through their relevance to inflammatory signaling pathways. CONCLUSIONS In patients undergoing CABG surgery, we found genetic polymorphisms in LY96 associated with decreased risk for postoperative AF.

Predictive ability of perioperative atrial fibrillation risk indices in cardiac surgery patients: a retrospective cohort study

“…This database was collected with a target sample size of n = 1004 patients undergoing various cardiac surgical procedures and has been detailed in previous manuscripts. 17 A STROBE diagram detailing cohort selection is shown in Fig. 1.…”

RNAs and Gene Expression Predicting Postoperative Atrial Fibrillation in Cardiac Surgery Patients Undergoing Coronary Artery Bypass Grafting

“…Kertai et al conducted a gene-wide association study in two cohorts of patients (diversity, n = 877 and validation, n = 304) to investigate the link of a genetic polymorphism in lymphocyte antigen 96 (LY96) with POAF incidence in CABG patients [43]. Based on SNPs selection criteria, they recognized only the minor allele of rs10504554, in the intronic region of the LY96, which exhibited a lower risk for POAF in both data sets (discovery data set: OR 0.48, 95% CI 0.34-0.68, p < 0.01, and replication dataset: OR 0.55, 95% CI 0.31-0.99, p = 0.046).…”

“…We also noted that most of the studies have shown only discovery group and the results were not validated in the independent validation group. Only two studies showed results for both the discovery and the validation groups [48], [43]. Most of the studies have patient population w/wo preexisting AF.…”

“…To date, the relationship between the function of miRNAs, circRNAs, and gene expressions with POAF risk development in CABG patients has not been thoroughly reviewed in published literature. In this narrative review, we report the available experimental evidence of several miRNAs such as miRNA-483-5p [34], miRNA-29a [35], miRNA-23a [36], miRNA-26a [36], miRNA-199a [16], miRNA-1 [37], and miRNA-133a [37], one circRNA: circRNA-025016 [38], and selected gene expressions such as mitochondrial DNA (mtDNA) [39,40], and other single nucleotide polymorphisms (SNPs) such as vesicular overexpressed in cancer-prosurvival protein 1 gene (VOPP1) [41], rs3740563 [42], rs10504554 [43], rs2249825 [44], rs4572292 [45], rs11198893 [45], rs10033464 [46,47], rs2200733 [46][47][48] and rs13143308 [48] used previously as potential elements predicting POAF risk following CABG surgery.…”

Utilisation de la pharmacogénomique et de la pharmacogénétique à l’unité de soins intensifs: un compte rendu narratif

“…The subsequent likely candidate gene(s) can then be studied in a confirmatory patient population. 32,60,61 Genetic information gained can be used in a preemptive fashion, with genome identification using polymorphisms that are known and available at the time of prescribing and accompanying clinical decision support incorporated into the electronic health record. 57 Investigators who prospectively performed genetic testing on patients scheduled for coronary arteriography recently reported using this method.…”