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Causal relationship between plasma metabolites and hypertension: A Mendelian randomization study
Fan Yang1, Yuan Wu1, Haixiang Zhu1
1Department of Cardiovascular Medicine, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Medicine
|October 7, 2025
Summary
This study used Mendelian randomization to investigate causal links between metabolites and hypertension. Some metabolites showed a causal relationship with hypertension, warranting further research into biological mechanisms.
Area of Science:
- Metabolomics
- Cardiovascular Genetics
- Epidemiology
Background:
- Observational studies suggest associations between metabolites and hypertension.
- Establishing a definitive causal link between metabolites and hypertension has been challenging.
- Genetic association studies provide a powerful tool to infer causality.
Purpose of the Study:
- To investigate the potential causal relationship between plasma metabolites and hypertension.
- To leverage Mendelian randomization to assess metabolite-hypertension associations.
- To identify specific metabolites that may causally influence hypertension risk.
Main Methods:
- Mendelian randomization analysis utilizing genome-wide association study (GWAS) summary statistics.
- GWAS data for over 2000 plasma metabolites from three studies.
- GWAS data for hypertension from two large-scale studies (n > 120,000).
- Inverse variance weighting (IVW) method for effect estimation.
- Bonferroni correction for multiple testing adjustment.
Main Results:
- Several metabolites were found to have a statistically significant causal effect on hypertension.
- Increased levels of taurochenodeoxycholate, 1-dihomo-linolenoyl-GPC, N-acetylphenylalanine, and dihomo-linolenate were associated with higher hypertension risk.
- Decreased levels of 2-hydroxyoctanoate, 1-docosapentaenoyl-GPC, X-11538, gamma-glutamyl-alpha-lysine, and 2-butenoylglycine were associated with lower hypertension risk.
Conclusions:
- This Mendelian randomization study provides evidence for a causal relationship between specific metabolites and hypertension.
- Identified metabolites may serve as potential therapeutic targets or biomarkers for hypertension.
- Further research is needed to elucidate the underlying biological pathways connecting these metabolites to hypertension.
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