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KMID : 0368120230530070472
Korean Circulation Journal
2023 Volume.53 No. 7 p.472 ~ p.479
Association Between Serum Bilirubin and Atrial Fibrillation: A Mendelian Randomization Study
Kim Si-Woo

Yang Jung-Ho
Kweon Sun-Seog
Lee Young-Hoon
Choi Seong-Woo
Ryu So-Yeon
Nam Hae-Sung
Kim Hye-Yeon
Shin Min-Ho
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 non-causal and affected by reverse causality or unmeasured confounding.
KEYWORD
Atrial fibrillation, Bilirubin, Mendelian randomization analysis, Causality
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