Exploring genetic causal relationships between spinal cord injury and glioma: a Mendelian randomization study
Abstract Background Gliomas and spinal cord injuries represent significant health challenges with potential shared genetic underpinnings. Understanding the causal genetic relationships between these conditions could provide valuable insights for targeted therapeutic interventions. This study aimed t...
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| Format: | Article |
| Language: | English |
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Springer
2025-06-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02919-z |
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| author | Guangbiao Li Jingquan Li Chaoen Hua Dachuan Pan Yonghong Li Huafang Hu Gang Wu |
| author_facet | Guangbiao Li Jingquan Li Chaoen Hua Dachuan Pan Yonghong Li Huafang Hu Gang Wu |
| author_sort | Guangbiao Li |
| collection | DOAJ |
| description | Abstract Background Gliomas and spinal cord injuries represent significant health challenges with potential shared genetic underpinnings. Understanding the causal genetic relationships between these conditions could provide valuable insights for targeted therapeutic interventions. This study aimed to investigate potential causal genetic associations between spinal cord injury and glioma using Mendelian Randomization approaches. Methods We employed Mendelian Randomization (MR) to examine potential genetic associations between spinal cord injury and glioma. Four SNPs (rs1358980, rs217992, rs789990, and rs158541) were used as instrumental variables, identified from the FinnGen R11 release’s “finngen_R11_C3_GBM_EXALLC” dataset. We applied three MR statistical approaches: MR Egger regression, Inverse Variance Weighted (IVW), and Weighted mode. Additionally, we analyzed gene expression patterns using RNA-sequencing data from TCGA and GEO databases, performed machine learning-based risk stratification, and validated our findings using single-cell RNA sequencing data from glioma patient tissues (GSE131928). Results Forest plot analyses revealed that while individual SNPs did not show significant effects on spinal cord injury (confidence intervals crossing zero), different MR methods yielded varying results. The MR Egger method demonstrated a positive correlation trend between glioma-associated genetic factors and spinal cord injury risk, while other methods showed more gradual effects. The MR analysis with the finngen_R11_C3_GBM_EXALLC genetic instrument yielded odds ratios close to 1.000 across all statistical methods (MR Egger: OR = 1.001, 95% CI 0.997–1.004, p = 0.759; IVW: OR = 1.000, 95% CI 1.000–1.000, p = 0.634), suggesting no significant causal relationship. Heterogeneity test results indicated moderate heterogeneity. Additionally, risk stratification analysis revealed significant differences in immune cell infiltration, gene expression patterns, and survival outcomes between high-risk and low-risk groups. Conclusion Our comprehensive analysis using Mendelian randomization provides evidence of complex genetic relationships between glioma and spinal cord injury. |
| format | Article |
| id | doaj-art-a015d5d798054f10b2293557547b2bd2 |
| institution | OA Journals |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-a015d5d798054f10b2293557547b2bd22025-08-20T02:37:14ZengSpringerDiscover Oncology2730-60112025-06-0116111910.1007/s12672-025-02919-zExploring genetic causal relationships between spinal cord injury and glioma: a Mendelian randomization studyGuangbiao Li0Jingquan Li1Chaoen Hua2Dachuan Pan3Yonghong Li4Huafang Hu5Gang Wu6Department of Neurosurgery, Liuzhou Traditional Chinese Medicine HospitalDepartment of Neurosurgery, Liuzhou Traditional Chinese Medicine HospitalDepartment of Neurosurgery, Liuzhou Traditional Chinese Medicine HospitalDepartment of Neurosurgery, Liuzhou Traditional Chinese Medicine HospitalDepartment of Radiology, Liuzhou Traditional Chinese Medicine HospitalDepartment of Radiology, Liuzhou Traditional Chinese Medicine HospitalDepartment of Neurosurgery, Liuzhou Traditional Chinese Medicine HospitalAbstract Background Gliomas and spinal cord injuries represent significant health challenges with potential shared genetic underpinnings. Understanding the causal genetic relationships between these conditions could provide valuable insights for targeted therapeutic interventions. This study aimed to investigate potential causal genetic associations between spinal cord injury and glioma using Mendelian Randomization approaches. Methods We employed Mendelian Randomization (MR) to examine potential genetic associations between spinal cord injury and glioma. Four SNPs (rs1358980, rs217992, rs789990, and rs158541) were used as instrumental variables, identified from the FinnGen R11 release’s “finngen_R11_C3_GBM_EXALLC” dataset. We applied three MR statistical approaches: MR Egger regression, Inverse Variance Weighted (IVW), and Weighted mode. Additionally, we analyzed gene expression patterns using RNA-sequencing data from TCGA and GEO databases, performed machine learning-based risk stratification, and validated our findings using single-cell RNA sequencing data from glioma patient tissues (GSE131928). Results Forest plot analyses revealed that while individual SNPs did not show significant effects on spinal cord injury (confidence intervals crossing zero), different MR methods yielded varying results. The MR Egger method demonstrated a positive correlation trend between glioma-associated genetic factors and spinal cord injury risk, while other methods showed more gradual effects. The MR analysis with the finngen_R11_C3_GBM_EXALLC genetic instrument yielded odds ratios close to 1.000 across all statistical methods (MR Egger: OR = 1.001, 95% CI 0.997–1.004, p = 0.759; IVW: OR = 1.000, 95% CI 1.000–1.000, p = 0.634), suggesting no significant causal relationship. Heterogeneity test results indicated moderate heterogeneity. Additionally, risk stratification analysis revealed significant differences in immune cell infiltration, gene expression patterns, and survival outcomes between high-risk and low-risk groups. Conclusion Our comprehensive analysis using Mendelian randomization provides evidence of complex genetic relationships between glioma and spinal cord injury.https://doi.org/10.1007/s12672-025-02919-zMendelian randomizationGliomaSpinal cord injuryGenetic associationSNPsRisk stratification |
| spellingShingle | Guangbiao Li Jingquan Li Chaoen Hua Dachuan Pan Yonghong Li Huafang Hu Gang Wu Exploring genetic causal relationships between spinal cord injury and glioma: a Mendelian randomization study Discover Oncology Mendelian randomization Glioma Spinal cord injury Genetic association SNPs Risk stratification |
| title | Exploring genetic causal relationships between spinal cord injury and glioma: a Mendelian randomization study |
| title_full | Exploring genetic causal relationships between spinal cord injury and glioma: a Mendelian randomization study |
| title_fullStr | Exploring genetic causal relationships between spinal cord injury and glioma: a Mendelian randomization study |
| title_full_unstemmed | Exploring genetic causal relationships between spinal cord injury and glioma: a Mendelian randomization study |
| title_short | Exploring genetic causal relationships between spinal cord injury and glioma: a Mendelian randomization study |
| title_sort | exploring genetic causal relationships between spinal cord injury and glioma a mendelian randomization study |
| topic | Mendelian randomization Glioma Spinal cord injury Genetic association SNPs Risk stratification |
| url | https://doi.org/10.1007/s12672-025-02919-z |
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