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Epidemiol Health > Accepted Articles
Epidemiology and Health 2019;e2019034.
DOI: https://doi.org/10.4178/epih.e2019034    [Accepted] Published online Jul 12, 2019.
Bilirubin and risk of ischemic heart disease in Korea: A two-sample Mendelian randomization study
Christina Jeon1,2  , Ji-Young Lee1  , Sun Ju Lee1,2  , Keum Ji Jung1  , Heejin Kimm1  , Sun Ha Jee1 
1Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea
2Department of Public Health, Graduate School, Yonsei University, Seoul, Korea
Correspondence  Ji-Young Lee ,Tel: 02-2228-1541, Email: sidea7@yuhs.ac
Received: Apr 2, 2019  Accepted after revision: Jul 12, 2019
Bilirubin is an endogenous antioxidant which protects cells against oxidative stress. Increased plasma levels of bilirubin have been associated with reduced risk of ischemic heart disease (IHD) in previous studies. Nonetheless, whether the associations reflect a true protective effect of bilirubin on IHD, rather than confounding or reverse causation remains unknown. Therefore, we applied the two-sample Mendelian randomization to evaluate a causal association between bilirubin levels and IHD risk among Korean populations.
A total of five genetic variants—TRPM8 (rs10490012), USP40 (rs12993249), (ATG16L1 (rs2119503), SLCO1B1 (rs4149014), and SLCO1B3 (rs73233620)—were selected as genetic instruments for serum bilirubin levels using a community-based cohort, the Korean Genome and Epidemiology Study (KoGES) comprising 33,598 subjects. Then, we evaluated their impact on ischemic heart disease using the Korean Cancer Prevention Study-II (KCPS-II) cohort.
Among five instrumental variables which showed significant associations with serum bilirubin levels, rs12993249 (USP40) showed the most significant association with serum bilirubin levels (p<2.36x10-105). However, we found no significant association between serum bilirubin levels and IHD. Sensitivity analyses demonstrated consistent association, suggesting robustness of our observation.
Using two-sample Mendelian randomization, we found no association between serum bilirubin levels and IHD. Further studies that confirm the observed interactions among other ethnicities are warranted.
Keywords: Bilirubin; Ischemic heart disease; Two-sample Mendelian randomization study


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