Epidemiol Health.  2019;41:e2019034. 10.4178/epih.e2019034.

Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study

Affiliations
  • 1Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea. sidea7@yuhs.ac
  • 2Department of Public Health, Graduate School, Yonsei University, Seoul, Korea.

Abstract


OBJECTIVES
Bilirubin is an endogenous antioxidant that protects cells against oxidative stress. Increased plasma levels of bilirubin have been associated with a reduced risk of ischemic heart disease (IHD) in previous studies. Nonetheless, whether those associations reflect a true protective effect of bilirubin on IHD, rather than confounding or reverse causation, remains unknown. Therefore, we applied two-sample Mendelian randomization to evaluate the causal association between bilirubin levels and IHD risk in a Korean population.
METHODS
A total of 5 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, comprising 33,598 subjects. We then evaluated their impact on IHD using the Korean Cancer Prevention Study-II cohort.
RESULTS
Among the 5 instrumental variables that showed significant associations with serum bilirubin levels, rs12993249 (USP40) showed the most significant association (p<2.36×10

Keyword

Bilirubin; Myocardial ischemia; Two-sample Mendelian randomization study; Korea

MeSH Terms

Bilirubin*
Cohort Studies
Epidemiology
Genome
Korea*
Myocardial Ischemia*
Oxidative Stress
Plasma
Random Allocation*
Bilirubin
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