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

ABSTRACT: 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 ?-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.

SUBMITTER: Kertai MD

PROVIDER: S-EPMC4809141 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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

Kertai Miklos D MD Li Yi-Ju YJ Ji Yunqi Y Qi Wenjing W Lombard Frederick W FW Shah Svati H SH Kraus William E WE Stafford-Smith Mark M Newman Mark F MF Milano Carmelo A CA Waldron Nathan N Podgoreanu Mihai V MV Mathew Joseph P JP

American heart journal 20150617 3

<h4>Background</h4>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.<h4>Methods</h4>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 lo ...[more]

PMID: 26385043

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Project description:BackgroundPostoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery. While thyroid dysfunction can predict POAF, the association between preoperative serum free triiodothyronine (FT3) levels and POAF in patients undergoing off-pump coronary artery bypass (OPCAB) grafting remains unclear. This study aimed to investigate the relationship between preoperative FT3 levels and POAF in OPCAB patients.MethodsThis prospective observational study included patients with sinus rhythm and no history of atrial fibrillation or thyroid disease who underwent OPCAB and FT3 testing at the Tianjin Chest Hospital from June 2021 to March 2023. The relationship between FT3 level and POAF was evaluated using restricted cubic spline. Cox proportional hazards regression models were used to analyze the associations between FT3 concentration categories [low T3 syndrome (LT3S) (FT3 below the normal range), low normal FT3 (3.10-4.59 pmol/L), high normal FT3 (4.60-6.80 pmol/L)] and POAF, adjusting for potential confounders. Stratified analyses were performed to assess effect modification by gender and age (<60 vs. ≥60 years old).ResultsAmong 875 patients, 259 (29.6%) developed POAF within 2 days after surgery. Restricted cubic spline analysis showed an S-shaped association between FT3 concentration and POAF risk. Compared to the low normal FT3 group, LT3S was associated with an increased risk of POAF [hazard ratio (HR), 1.41; 95% confidence interval (CI): 1.90-2.19], while high normal FT3 was associated with a decreased risk (HR, 0.72; 95% CI: 0.51-0.99). The association between FT3 and increased POAF risk was more pronounced in patients aged ≥60 years (HR, 1.41; 95% CI: 1.89-2.22).ConclusionsPreoperative FT3 levels most likely could predict POAF risk after OPCAB, especially in patients aged 60 years and older. Measuring FT3 preoperatively may identify high-risk patients benefiting from close monitoring and prophylactic treatment. Further investigation of thyroid hormone replacement therapy for LT3S is warranted.

Project description:BackgroundPostoperative atrial fibrillation (POAF) is the most common cardiac dysrhythmia to occur after coronary artery bypass grafting (CABG). However, the risk factors for new-onset POAF after CABG during the perioperative period have yet to be clearly defined. Accordingly, the aim of our systematic review was to evaluate the perioperative predictors of new-onset POAF after isolated CABG.MethodOur review methods adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We searched seven electronic databases (PubMed, Embase, CINAHL, PsycArticles, Cochrane, Web of Science, and SCOPUS) to identify all relevant English articles published up to January 2020. Identified studies were screened independently by two researchers for selection, according to predefined criteria. The Newcastle-Ottawa Scale was used to evaluate the quality of studies retained.ResultsAfter screening, nine studies were retained for analysis, including 4798 patients, of whom 1555 (32.4%) experienced new-onset POAF after CABG. The incidence rate of new-onset POAF ranged between 17.3% and 47.4%. The following risk factors were identified: old age (p < 0.001), a high preoperative serum creatinine level (p = 0.001), a low preoperative hemoglobin level (p = 0.007), a low left ventricle ejection fraction in Asian patients (p = 0.001), essential hypertension (p < 0.001), chronic obstructive pulmonary disease (p = 0.010), renal failure (p = 0.009), cardiopulmonary bypass use (p = 0.002), perfusion time (p = 0.017), postoperative use of inotropes (p < 0.001), postoperative renal failure (p = 0.001), and re-operation (p = 0.005). All studies included in the analysis were of good quality.ConclusionsThe risk factors identified in our review could be used to improve monitoring of at-risk patients for early detection and treatment of new-onset POAF after CABG, reducing the risk of other complications and negative clinical outcomes.

Dataset Information

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

Publications

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

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