Research Paper Volume 16, Issue 9 pp 8306—8319
Deciphering the causal relationship between plasma and cerebrospinal fluid metabolites and glioblastoma multiforme: a Mendelian Randomization study
- 1 Department of Neurosurgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde, Hunan 415003, People’s Republic of China
Received: December 26, 2023 Accepted: April 10, 2024 Published: May 10, 2024
https://doi.org/10.18632/aging.205818How to Cite
Copyright: © 2024 Zhou and Leng. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Glioblastoma Multiforme (GBM) is one of the most aggressive and fatal brain cancers. The study of metabolites could be crucial for understanding GBM’s biology and reveal new treatment strategies.
Methods: The GWAS data for GBM were sourced from the FinnGen database. A total of 1400 plasma metabolites were collected from the GWAS Catalog dataset. The cerebrospinal fluid (CSF) metabolites data were collected from subsets of participants in the WADRC and WRAP studies. We utilized the inverse variance weighting (IVW) method as the primary tool to explore the causal relationship between metabolites in plasma and CSF and glioblastoma, ensuring the exclusion of instances with horizontal pleiotropy. Additionally, four supplementary analytical methods were applied to reinforce our findings. Aberrant results were identified and omitted based on the outcomes of the leave-one-out sensitivity analysis. Conclusively, a reverse Mendelian Randomization analysis was also conducted to further substantiate our results.
Results: The study identified 69 plasma metabolites associated with GBM. Of these, 40 metabolites demonstrated a significant positive causal relationship with GBM, while 29 exhibited a significant negative causal association. Notably, Trimethylamine N-oxide (TMAO) levels in plasma, not CSF, were found to be a significant exposure factor for GBM (OR = 3.1627, 95% CI = (1.6347, 6.1189), P = 0.0006). The study did not find a reverse causal relationship between GBM and plasma TMAO levels.
Conclusions: This research has identified 69 plasma metabolites potentially associated with the incidence of GBM, among which TMAO stands out as a promising candidate for an early detectable biomarker for GBM.
Abbreviations
GBM: Glioblastoma Multiforme; TMAO: Trimethylamine N-oxide; MR: Mendelian Randomization; GWAS: Genome-Wide Association Study; IVW: Inverse Variance Weighted; WM: Weighted Median; IVs: Instrumental Variables; SNPs: Single Nucleotide Polymorphisms; MR-PRESSO: Mendelian Randomization Pleiotropy RESidual Sum and Outlier; IEU: Integrative Epidemiology Unit; CSF: Cerebrospinal fluid.