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Causal relationship between inflammatory proteins and glioblastoma: a two-sample bi‑directional mendelian
Xiang Lin1,2,3, Wei Gao2,3, Chen Huang4
1Department of Pathology, The Second Xiangya Hospital, Central South University Changsha, Hunan, China.
Frontiers in Genetics
|May 24, 2024
Summary
Mendelian randomization revealed that lower fibroblast growth factor 21 (FGF21) levels are linked to glioblastoma risk. Glioblastoma also influences inflammatory proteins like CXCL9 and IL-33, offering new insights into its development.
Area of Science:
- Neuro-oncology
- Genetics
- Immunology
Background:
- Observational studies suggest a link between glioblastoma and circulating inflammatory proteins.
- Causal relationships require further investigation using genetic approaches.
- Understanding these links is crucial for glioblastoma pathogenesis research.
Purpose of the Study:
- To investigate the causal impact of circulating inflammation-related proteins on glioblastoma risk using Mendelian randomization.
- To explore the reverse causal relationship where glioblastoma may influence protein levels.
- To validate findings using transcriptomic data and elucidate underlying mechanisms.
Main Methods:
- Mendelian randomization (MR) analysis utilizing genome-wide association study (GWAS) summary statistics for 91 inflammation-related proteins and glioblastoma.
- Inverse variance weighted (IVW) method as primary analysis, supplemented by MR-Egger, weighted median, and other MR methods.
- Sensitivity analyses for heterogeneity and pleiotropy, reverse MR, and TCGA transcriptomic data analysis.
Main Results:
- Forward MR identified an association between elevated Cystatin D and decreased fibroblast growth factor 21 (FGF21) with glioblastoma risk.
- Reverse MR indicated that glioblastoma may increase circulating levels of C-X-C motif chemokine 9 (CXCL9) and Interleukin-33 (IL-33).
- Transcriptomic data showed inverse association for FGF21 and positive associations for CXCL9 and IL-33 with glioblastoma risk.
Conclusions:
- Fibroblast growth factor 21 (FGF21) is a significant factor in glioblastoma susceptibility.
- Glioblastoma influences inflammatory protein expression (CXCL9, IL-33), impacting disease mechanisms.
- Findings provide novel insights into glioblastoma genesis and potential therapeutic targets.
