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

Epidemiol Health. 2019:41:e2019034. doi: 10.4178/epih.e2019034. Epub 2019 Jul 12.

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 communitybased 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<2.36×10-105). However, we found no significant association between serum bilirubin levels and IHD. Sensitivity analyses demonstrated a consistent association, suggesting that our observations were robust.

Conclusions: 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; Korea; Myocardial ischemia; Two-sample Mendelian randomization study.

MeSH terms

  • Bilirubin / blood*
  • Causality
  • Cohort Studies
  • Female
  • Genetic Variation
  • Humans
  • Male
  • Mendelian Randomization Analysis
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / epidemiology*
  • Myocardial Ischemia / genetics
  • Republic of Korea / epidemiology

Substances

  • Bilirubin