Korean Circ J.  2023 Jul;53(7):472-479. 10.4070/kcj.2023.0003.

Association Between Serum Bilirubin and Atrial Fibrillation: A Mendelian Randomization Study

• Kim SW
• Yang JH
• Kweon SS
• Lee YH
• Choi SW
• Ryu SY
• Nam HS
• Kim HY
• Shin MH

• KMID: 2545132
• DOI: http://doi.org/10.4070/kcj.2023.0003

Abstract

Background and Objectives
The association between bilirubin and atrial fibrillation (AF) has been evaluated previously in observational studies but with contradictory results. This study evaluated the causal association between serum bilirubin level and AF using Mendelian randomization (MR) analysis.
Methods
This cross-sectional study includes 8,977 participants from the Dong-gu Study. In the observational analysis, multivariate logistic regression was performed to evaluate the association between bilirubin and prevalent AF. To evaluate the causal association between bilirubin and AF, MR analysis was conducted by using the UGT1A1 rs11891311 and rs4148323 polymorphisms as instrumental variables.
Results
Elevated serum bilirubin levels were associated with an increased risk for AF in observational analysis (total bilirubin: odds ratio [OR], 1.31; 95% confidence interval [95% CI], 1.15–1.48 per 1 standard deviation [SD]; direct bilirubin: OR, 1.31; 95% CI, 1.18–1.46 per 1 SD), whereas the genetically predicted serum bilirubin levels in MR analysis did not show this association (total bilirubin: OR, 1.02; 95% CI, 0.67–1.53 per 1 SD; direct bilirubin: OR, 1.03; 95% CI, 0.61–1.73 per 1 SD).
Conclusions
Genetically predicted bilirubin levels were not associated with prevalent AF. Thus, the observational association between serum bilirubin levels and AF may be noncausal and affected by reverse causality or unmeasured confounding.

Keyword

Atrial fibrillation; Bilirubin; Mendelian randomization analysis; Causality

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