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Background <p>Recent studies have suggested that serum metabolites and cerebrospinal fluid (CSF) metabolites play a role in aneurysmal subarachnoid hemorrhage (aSAH).</p> Methods <p>A Mendelian randomization (MR) study was conducted to elucidate the potential causal effect of serum metabolites and CSF metabolites on aSAH. Genetic information related to exposure and outcome was obtained from the GWAS summary data. To evaluate the potential causal relationship between them, we adopted IVW as the preferred method, supplemented by weighted median and MR Egger. In addition, we performed sensitivity analyses evaluate the stability of the MR results. Metabolic pathways analysis and colocalization analysis were applied to complement the significant results.</p> Results <p>Our findings defined 21 suggestive causal relationships between serum, CSF metabolites and aSAH. ADSGEGDFXAEGGGVR (OR 0.64, 95%CI 0.43–0.97, <i>p</i> = 0.03), alpha-hydroxyisovalerate (OR 0.40, 95%CI 0.20–0.80, <i>p</i> = 0.01) and Methionine sulfoxide (OR 0.77, 95%CI 0.62–0.95, <i>p</i> = 0.02) are independent related factors. Metabolic pathway analysis showed that 4 metabolites and their associated metabolic pathways have significant effects on aSAH. Through co-localization analysis, it was found that SLC22A5 are shared risk sites between metabolites and aSAH.</p> Conclusion <p>Our study identified a total of 21 metabolites that are causally related to aSAH, including 3 separate elements. This may offer fresh insights into aSAH biomarkers and therapeutic targets through specific metabolites.</p>

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Metabolome Wide Mendelian Randomization Assessing the Causal Relationship Between Serum Metabolites, Cerebrospinal Metabolites, and Aneurysmal Subarachnoid Hemorrhage

  • 期刊论文

  • 发表日期：

    2026年3月26日

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  • Bingyi Song,
  • Youjia Qiu,
  • Minjia Xie,
  • Yuchen Tao,
  • Ziqian Yin,
  • Menghan Wang,
  • Na Ji,
  • Xinlin Tang,
  • Zhouqing Chen,
  • Zhong Wang

摘要

Background

Recent studies have suggested that serum metabolites and cerebrospinal fluid (CSF) metabolites play a role in aneurysmal subarachnoid hemorrhage (aSAH).

Methods

A Mendelian randomization (MR) study was conducted to elucidate the potential causal effect of serum metabolites and CSF metabolites on aSAH. Genetic information related to exposure and outcome was obtained from the GWAS summary data. To evaluate the potential causal relationship between them, we adopted IVW as the preferred method, supplemented by weighted median and MR Egger. In addition, we performed sensitivity analyses evaluate the stability of the MR results. Metabolic pathways analysis and colocalization analysis were applied to complement the significant results.

Results

Our findings defined 21 suggestive causal relationships between serum, CSF metabolites and aSAH. ADSGEGDFXAEGGGVR (OR 0.64, 95%CI 0.43–0.97, p = 0.03), alpha-hydroxyisovalerate (OR 0.40, 95%CI 0.20–0.80, p = 0.01) and Methionine sulfoxide (OR 0.77, 95%CI 0.62–0.95, p = 0.02) are independent related factors. Metabolic pathway analysis showed that 4 metabolites and their associated metabolic pathways have significant effects on aSAH. Through co-localization analysis, it was found that SLC22A5 are shared risk sites between metabolites and aSAH.

Conclusion

Our study identified a total of 21 metabolites that are causally related to aSAH, including 3 separate elements. This may offer fresh insights into aSAH biomarkers and therapeutic targets through specific metabolites.