ArticleEpidemiology and health2024
Causal association between serum bilirubin and ischemic stroke: multivariable Mendelian randomization.
Article in Epidemiology and health, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Associations of bilirubin, albumin, and the ALBI index with gastric cancer risk: a smoking-stratified prospective cohort study in men.BMC gastroenterology · 2026Article
- Sex-specific in the nonlinear associations of hemoglobin glycation index and all-cause mortality in the general US adult population: results from NHANES 1999-2018.Nutrition & metabolism · 2026Article
- Association between De Ritis ratio and mortality in individuals with diabetes or prediabetes: evidence from NHANES (1999-2018).European journal of medical research · 2025Article
- Toward Precision Post-Stroke Rehabilitation Medicine: Integrating Molecular, Imaging, and Computational Biomarkers for Functional Outcome Prediction.Journal of clinical medicine · 2025Review
- Article
- Sex-Specific Associations of Total Bilirubin, ALBI, and PALBI with Lung Cancer Risk: Interactions with Smoking and Alcohol.Healthcare (Basel, Switzerland) · 2025Article
- Association Between Creatinine and Lung Cancer Risk in Men Smokers: A Comparative Analysis with Antioxidant Biomarkers from the KCPS-II Cohort.Antioxidants (Basel, Switzerland) · 2025Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesPrevious research has predominantly focused on total bilirubin levels without clearly distinguishing between direct and indirect bilirubin. In this study, the differences between these forms were examined, and their potential causal relationships with ischemic stroke were investigated.
methodsTwo-sample multivariable Mendelian randomization (MVMR) analysis was employed, extracting summary data on bilirubin from the Korean Cancer Prevention Study-II (n=159,844) and the Korean Genome and Epidemiology Study (n=72,299). Data on ischemic stroke were obtained from BioBank Japan (n=201,800). Colocalization analysis was performed, focusing on the UGT1A1, SLCO1B1, and SLCO1B3 genes, which are the primary loci associated with serum bilirubin levels.
resultsCrude 2-sample Mendelian randomization analysis revealed a significant negative association between total bilirubin levels and ischemic stroke. However, in MVMR analyses, only indirect bilirubin demonstrated a significant negative association with ischemic stroke (odds ratio, 0.76; 95% confidence interval, 0.59 to 0.98). Colocalization analysis did not identify a shared causal variant between the 3 genetic loci related to indirect bilirubin and the risk of ischemic stroke.
conclusionsOur study establishes a causal association between higher genetically determined levels of serum indirect bilirubin and reduced risk of ischemic stroke in an Asian population. Future research should include more in-depth analysis of shared genetic variants between indirect bilirubin and ischemic stroke.
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