Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study
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...
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Korean Society of Epidemiology
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doaj-e629a098e6214221a0f6e35ca69b821a2020-11-25T03:34:57ZengKorean Society of Epidemiology Epidemiology and Health2092-71932019-07-014110.4178/epih.e20190341049Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization studyChristina Jeon0Ji-Young Lee1Sun Ju Lee2Keum Ji Jung3Heejin Kimm4Sun Ha Jee5 Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, KoreaOBJECTIVES 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.http://e-epih.org/upload/pdf/epih-41-e2019034.pdfbilirubinmyocardial ischemiatwo-sample mendelian randomization studykorea |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christina Jeon Ji-Young Lee Sun Ju Lee Keum Ji Jung Heejin Kimm Sun Ha Jee |
spellingShingle |
Christina Jeon Ji-Young Lee Sun Ju Lee Keum Ji Jung Heejin Kimm Sun Ha Jee Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study Epidemiology and Health bilirubin myocardial ischemia two-sample mendelian randomization study korea |
author_facet |
Christina Jeon Ji-Young Lee Sun Ju Lee Keum Ji Jung Heejin Kimm Sun Ha Jee |
author_sort |
Christina Jeon |
title |
Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study |
title_short |
Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study |
title_full |
Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study |
title_fullStr |
Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study |
title_full_unstemmed |
Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study |
title_sort |
bilirubin and risk of ischemic heart disease in korea: a two-sample mendelian randomization study |
publisher |
Korean Society of Epidemiology |
series |
Epidemiology and Health |
issn |
2092-7193 |
publishDate |
2019-07-01 |
description |
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. |
topic |
bilirubin myocardial ischemia two-sample mendelian randomization study korea |
url |
http://e-epih.org/upload/pdf/epih-41-e2019034.pdf |
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