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Causal Associations Between Serum Bilirubin Levels and Decreased Stroke Risk: A Two-Sample Mendelian Randomization Study

Authors
 Yoonjeong Choi  ;  Sun Ju Lee  ;  Wes Spiller  ;  Keum Ji Jung  ;  Ji-Young Lee  ;  Heejin Kimm  ;  Joung Hwan Back  ;  Sunmi Lee  ;  Sun Ha Jee 
Citation
 ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, Vol.40(2) : 437-445, 2020 
Journal Title
 ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 
ISSN
 1079-5642 
Issue Date
2020
Keywords
bilirubin ; cardiovascular diseases ; causality ; single nucleotide polymorphism ; stroke
Abstract
OBJECTIVE: A number of epidemiological studies have reported that decreased serum bilirubin, an endogenous antioxidant, is associated with cardiovascular disease. However, previous Mendelian randomization analyses conducted using a single sample have shown no evidence of association. Approach and Results: A 2-sample summary Mendelian randomization study was performed by obtaining exposure and outcome data from separate nonoverlapping samples. We utilized data from the KoGES (Korean Genome and Epidemiology Study; n=25 406) and KCPS-II (Korean Cancer Prevention Study-II; n=14 541) biobank for serum bilirubin and stroke, respectively. Using KoGES, a total of 1784 single nucleotide polymorphisms associated with serum bilirubin levels were discovered using a genome-wide significance threshold (P<5×10-8), of which 10 single nucleotide polymorphisms were identified as independent (R2<0.005) and adopted as genetic instruments. From KCPS-II, total and ischemic stroke cases were identified (n=1489 and n=686), with 12 366 acting as controls. Various 2-sample summary Mendelian randomization methods were employed, with Mendelian randomization estimates showing an inverse causal association between serum bilirubin levels and total stroke risk (odds ratio, 0.481 [95% CI, 0.234-0.988]; P=0.046). This association increased in magnitude when restricting the analysis to ischemic stroke cases (odds ratio, 0.302 [95% CI, 0.105-0.868]; P=0.026). CONCLUSIONS: Our findings provide evidence of significant causal relationship between high levels of bilirubin and decreased stroke risk in Korean population in agreement with observational approaches. This highlights the potential for bilirubin to serve as a therapeutic target for oxidative stress-related diseases such as stroke and suggests that previous findings were not a consequence of unmeasured confounding.
Files in This Item:
T202000305.pdf Download
DOI
10.1161/ATVBAHA.119.313055
Appears in Collections:
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Kimm, Heejin(김희진) ORCID logo https://orcid.org/0000-0003-4526-0570
Lee, Ji Young(이지영) ORCID logo https://orcid.org/0000-0002-7784-1401
Jung, Keum Ji(정금지) ORCID logo https://orcid.org/0000-0003-4993-0666
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175288
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