Potential Causal Relationship Between Plasma and Cerebrospinal Fluid Metabolites and Meningioma: Two-Sample Mendelian Randomization Study

Abstract

Guangyu Du, Daikang Xu, Hai Zhao, Zhiyong Yan, Jianpeng Wang Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of ChinaCorrespondence: Zhiyong Yan, Department of Neurosurgery, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266000, People’s Republic of China, Email [email protected] Jianpeng Wang, Department of Neurosurgery, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266000, People’s Republic of China, Email [email protected]: Meningioma (MGM) is the most common benign intracranial tumor and ranks as the second most frequent intracranial tumor in terms of incidence, following malignant gliomas. Studying the metabolites in the serum and cerebrospinal fluid (CSF) of patients with MGM is crucial for understanding the underlying biological mechanisms, identifying new biomarkers, and developing novel therapeutic strategies.Methods: Mendelian randomization (MR) is a powerful analytical approach that leverages genetic variants to assess potential causal relationships between exposures and outcomes. In this study, MR analysis was used to investigate the causal relationships between 486 serum metabolites, 338 CSF metabolites, and MGM. Our MGM data was derived from the genome wide association studies (GWASs) dataset in the FinnGen database, comprising 1,835 cases of European ancestry and 377,674 controls. The data for 486 plasma metabolites was obtained from the GWAS catalog, and the data for 338 CSF metabolites was obtained from the Wisconsin Alzheimer’s Disease Research Center (WADRC) and Wisconsin Alzheimer’s Disease Prevention Registry (WRAP) study collections. We mainly utilized the Inverse Variance Weighted (IVW) approach to evaluate the causal association between metabolites and MGMs, supplemented by four additional methods to further validate and strengthen our findings. False discovery rate (FDR) correction was applied (q< 0.05) to control the false-positive rate.Results: Through MR analysis, the study identified 19 plasma metabolites and 17 CSF metabolites demonstrating potential causal associations with MGMs. Among these, 14 metabolites indicated positive causality with MGMs, while 22 metabolites displayed a remarkable negative causality. In particular, plasma levels of Glycerol 3−phosphate (G3P) (OR=4.76, 95% CI=1.02– 22.12, P=0.047) and Valine (OR=0.025, 95% CI=0.0020– 0.42, P=0.010) were found to exhibit the optimal efficacy. Multiple sensitivity analyses confirm the robustness of the results. The study found no evidence of a reverse causality between MGMs and the plasma levels of Glycerol 3−phosphate (G3P) and Valine.Conclusion: This study identified 36 metabolites associated with the incidence of MGMs, among which Glycerol 3-phosphate (G3P) and Valine are the most notable findings.Keywords: plasma, cerebrospinal fluid, meningioma, Mendelian randomization, metabolites

Keywords

• Plasma
• Cerebrospinal fluid
• Meningioma
• Mendelian randomization
• Metabolites