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Causal association between serum bilirubin and ischemic stroke: multivariable Mendelian randomization
Jong Won Shin1,2, Keum Ji Jung1,3, Mikyung Ryu4,5
1Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
Epidemiology and Health
|August 30, 2024
Summary
Higher levels of indirect bilirubin are linked to a lower risk of ischemic stroke. This study investigated the causal relationship between bilirubin types and stroke, finding a protective effect for indirect bilirubin.
Area of Science:
- Biochemistry and Genetics
- Neurology and Stroke Research
- Population Health Studies
Background:
- Previous research on bilirubin and stroke risk often overlooked the distinct roles of direct and indirect bilirubin.
- Understanding the specific contributions of bilirubin forms is crucial for accurate risk assessment and potential therapeutic strategies.
Purpose of the Study:
- To investigate the differential causal relationships between direct and indirect bilirubin and ischemic stroke risk.
- To differentiate the impact of bilirubin forms, moving beyond total bilirubin measurements.
Main Methods:
- Utilized two-sample multivariable Mendelian randomization (MVMR) analysis with large-scale Korean and Japanese population data.
- Included colocalization analysis focusing on key genes (UGT1A1, SLCO1B1, SLCO1B3) involved in bilirubin metabolism.
Main Results:
- Crude analysis showed total bilirubin negatively associated with ischemic stroke.
- MVMR analysis identified a significant negative association specifically for indirect bilirubin (OR, 0.76; 95% CI, 0.59-0.98).
- Colocalization analysis did not reveal shared causal variants between indirect bilirubin loci and ischemic stroke risk.
Conclusions:
- Established a genetically determined causal link between higher serum indirect bilirubin and reduced ischemic stroke risk in an Asian population.
- Highlights the importance of distinguishing bilirubin types in stroke research.
- Suggests further investigation into shared genetic factors between indirect bilirubin and ischemic stroke.
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