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Causal Association Between Cerebrospinal Fluid Metabolites and Stroke: A Mendelian Randomization Study
Xue Jiang1, Fei Xie1, Yiwei Sun2
1College of Chemistry and Life Science, Beijing University of Technology, Beijing, 100124, China.
Current Neurovascular Research
|January 2, 2026
Summary
Cerebrospinal fluid metabolites causally influence stroke subtypes, and stroke impacts metabolite levels, revealing bidirectional interactions. This highlights potential biomarkers for stroke diagnosis and precision medicine.
Area of Science:
- Neuroscience
- Metabolomics
- Genetics
Background:
- Stroke is a major global cause of death and disability.
- Cerebrospinal fluid (CSF) metabolites are linked to stroke, but causal roles are unclear.
Purpose of the Study:
- To investigate the causal relationships between CSF metabolites and stroke.
- To explore stroke's influence on CSF metabolic profiles.
Main Methods:
- Integrated genome-wide association study (GWAS) data with stroke outcomes.
- Utilized two-sample and reverse Mendelian randomization (MR) analyses for causal inference.
- Employed seven complementary MR methods to ensure robust findings.
Main Results:
- Identified 18 CSF metabolites associated with overall stroke risk and protection.
- Linked specific metabolites to ischemic, cardioembolic, large artery, and small vessel stroke subtypes.
- Found stroke causally influences certain CSF metabolites, indicating bidirectional interactions.
Conclusions:
- CSF metabolites play causal roles in stroke pathogenesis and subtypes.
- Stroke alters CSF metabolic profiles, suggesting complex bidirectional relationships.
- Identified potential biomarkers and therapeutic targets for stroke precision medicine.
