Causal effect between circulating metabolic markers and glioma: a bidirectional, two-sample, Bayesian weighted Mendelian randomization

Abstract Glioma is the most common malignant tumor in the central nervous system with significant challenges for its treatment and prognosis. Based on publicly available genome-wide association study data, this study employed a bidirectional, two-sample Mendelian randomization (MR) analysis, combine...

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Main Authors: Jiachen Wang, Chengzhuo Wang, Shenglan Li, Mengqian Huang, Rong Zhang, Yuxiao Chen, Zhuang Kang, Wenbin Li
Format: Article
Language:English
Published: Springer 2025-03-01
Series:Discover Oncology
Online Access:https://doi.org/10.1007/s12672-025-02050-z
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author Jiachen Wang
Chengzhuo Wang
Shenglan Li
Mengqian Huang
Rong Zhang
Yuxiao Chen
Zhuang Kang
Wenbin Li
author_facet Jiachen Wang
Chengzhuo Wang
Shenglan Li
Mengqian Huang
Rong Zhang
Yuxiao Chen
Zhuang Kang
Wenbin Li
author_sort Jiachen Wang
collection DOAJ
description Abstract Glioma is the most common malignant tumor in the central nervous system with significant challenges for its treatment and prognosis. Based on publicly available genome-wide association study data, this study employed a bidirectional, two-sample Mendelian randomization (MR) analysis, combined with Bayesian weighted MR, to investigate the causal effect of 233 circulating metabolic traits on glioma and its subtypes, with the expectation of discovering new diagnostic and therapeutic targets. The MR study revealed that the Total cholesterol to total lipids ratio in large VLDL and the Ratio of polyunsaturated fatty acids to total fatty acids (PUFAbyFA) are risk factors for glioma, while free cholesterol or phospholipids in small HDL are protective against glioma. The free cholesterol to total lipids ratio in IDL, the ratios of total cholesterol or cholesteryl esters to total lipids in small or medium VLDL, as well as linoleic acid (LA 18:2), phosphatidylcholine, and sphingomyelins levels are risk factors for non-GBM glioma. Free cholesterol in small HDL is identified as a protective factor for non-GBM glioma. The results were robust to sensitivity analyses and Bayesian weighted mendelian randomization. The causal effects of glioma on circulating metabolites were explored through reverse mendelian randomization. The results provide potential biomarkers for the early diagnosis and treatment of glioma.
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spelling doaj-art-c0d40d5daa35448db4fd8a7bbcd97a6a2025-08-20T02:56:07ZengSpringerDiscover Oncology2730-60112025-03-0116111410.1007/s12672-025-02050-zCausal effect between circulating metabolic markers and glioma: a bidirectional, two-sample, Bayesian weighted Mendelian randomizationJiachen Wang0Chengzhuo Wang1Shenglan Li2Mengqian Huang3Rong Zhang4Yuxiao Chen5Zhuang Kang6Wenbin Li7Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical UniversityAbstract Glioma is the most common malignant tumor in the central nervous system with significant challenges for its treatment and prognosis. Based on publicly available genome-wide association study data, this study employed a bidirectional, two-sample Mendelian randomization (MR) analysis, combined with Bayesian weighted MR, to investigate the causal effect of 233 circulating metabolic traits on glioma and its subtypes, with the expectation of discovering new diagnostic and therapeutic targets. The MR study revealed that the Total cholesterol to total lipids ratio in large VLDL and the Ratio of polyunsaturated fatty acids to total fatty acids (PUFAbyFA) are risk factors for glioma, while free cholesterol or phospholipids in small HDL are protective against glioma. The free cholesterol to total lipids ratio in IDL, the ratios of total cholesterol or cholesteryl esters to total lipids in small or medium VLDL, as well as linoleic acid (LA 18:2), phosphatidylcholine, and sphingomyelins levels are risk factors for non-GBM glioma. Free cholesterol in small HDL is identified as a protective factor for non-GBM glioma. The results were robust to sensitivity analyses and Bayesian weighted mendelian randomization. The causal effects of glioma on circulating metabolites were explored through reverse mendelian randomization. The results provide potential biomarkers for the early diagnosis and treatment of glioma.https://doi.org/10.1007/s12672-025-02050-z
spellingShingle Jiachen Wang
Chengzhuo Wang
Shenglan Li
Mengqian Huang
Rong Zhang
Yuxiao Chen
Zhuang Kang
Wenbin Li
Causal effect between circulating metabolic markers and glioma: a bidirectional, two-sample, Bayesian weighted Mendelian randomization
Discover Oncology
title Causal effect between circulating metabolic markers and glioma: a bidirectional, two-sample, Bayesian weighted Mendelian randomization
title_full Causal effect between circulating metabolic markers and glioma: a bidirectional, two-sample, Bayesian weighted Mendelian randomization
title_fullStr Causal effect between circulating metabolic markers and glioma: a bidirectional, two-sample, Bayesian weighted Mendelian randomization
title_full_unstemmed Causal effect between circulating metabolic markers and glioma: a bidirectional, two-sample, Bayesian weighted Mendelian randomization
title_short Causal effect between circulating metabolic markers and glioma: a bidirectional, two-sample, Bayesian weighted Mendelian randomization
title_sort causal effect between circulating metabolic markers and glioma a bidirectional two sample bayesian weighted mendelian randomization
url https://doi.org/10.1007/s12672-025-02050-z
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