Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival
Abstract Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) c...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55919-6 |
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| author | Linda Kachuri Geno A. Guerra Taishi Nakase George A. Wendt Helen M. Hansen Annette M. Molinaro Paige Bracci Lucie McCoy Terri Rice John K. Wiencke Jeanette E. Eckel-Passow Robert B. Jenkins Margaret Wrensch Stephen S. Francis |
| author_facet | Linda Kachuri Geno A. Guerra Taishi Nakase George A. Wendt Helen M. Hansen Annette M. Molinaro Paige Bracci Lucie McCoy Terri Rice John K. Wiencke Jeanette E. Eckel-Passow Robert B. Jenkins Margaret Wrensch Stephen S. Francis |
| author_sort | Linda Kachuri |
| collection | DOAJ |
| description | Abstract Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.25, p = 0.005), especially tumors with isocitrate dehydrogenase (IDH) mutations (OR = 1.38, p = 0.007) and IDHmut 1p/19q intact (IDHmut-intact OR = 1.53, p = 0.004) tumors. Genetically inferred increased counts of lymphocytes (IDHmut-intact OR = 0.70, p = 0.004) and neutrophils (IDHmut OR = 0.69, p = 0.019; IDHmut-intact OR = 0.60, p = 0.009) show inverse associations with risk, which may reflect enhanced immune-surveillance. Considering survival, we observe higher mortality risk in patients with IDHmut 1p/19q with genetically predicted increased counts of lymphocytes (hazard ratio (HR) = 1.65, 95% CI: 1.24–2.20), neutrophils (HR = 1.49, 1.13–1.97), and eosinophils (HR = 1.59, 1.18–2.14). Polygenic scores for blood cell traits are also differentially associated with 17 tumor immune microenvironment features in a subtype-specific manner, including signatures related to interferon signaling, PD-1 expression, and T-cell/Cytotoxic responses. Our findings highlight immune-mediated susceptibility mechanisms with potential disease management implications. |
| format | Article |
| id | doaj-art-521a4eac2c9f468f8c8baca161204692 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-521a4eac2c9f468f8c8baca1612046922025-01-19T12:31:18ZengNature PortfolioNature Communications2041-17232025-01-0116111310.1038/s41467-025-55919-6Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survivalLinda Kachuri0Geno A. Guerra1Taishi Nakase2George A. Wendt3Helen M. Hansen4Annette M. Molinaro5Paige Bracci6Lucie McCoy7Terri Rice8John K. Wiencke9Jeanette E. Eckel-Passow10Robert B. Jenkins11Margaret Wrensch12Stephen S. Francis13Department of Epidemiology & Population Health, Stanford University School of MedicineDepartment of Neurological Surgery, University of California San FranciscoDepartment of Epidemiology & Population Health, Stanford University School of MedicineDepartment of Neurological Surgery, University of California San FranciscoDepartment of Neurological Surgery, University of California San FranciscoDepartment of Neurological Surgery, University of California San FranciscoDepartment of Epidemiology & Biostatistics, University of California San FranciscoDepartment of Neurological Surgery, University of California San FranciscoDepartment of Neurological Surgery, University of California San FranciscoDepartment of Neurological Surgery, University of California San FranciscoDivision of Biomedical Statistics and Informatics, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Neurological Surgery, University of California San FranciscoDepartment of Neurological Surgery, University of California San FranciscoAbstract Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.25, p = 0.005), especially tumors with isocitrate dehydrogenase (IDH) mutations (OR = 1.38, p = 0.007) and IDHmut 1p/19q intact (IDHmut-intact OR = 1.53, p = 0.004) tumors. Genetically inferred increased counts of lymphocytes (IDHmut-intact OR = 0.70, p = 0.004) and neutrophils (IDHmut OR = 0.69, p = 0.019; IDHmut-intact OR = 0.60, p = 0.009) show inverse associations with risk, which may reflect enhanced immune-surveillance. Considering survival, we observe higher mortality risk in patients with IDHmut 1p/19q with genetically predicted increased counts of lymphocytes (hazard ratio (HR) = 1.65, 95% CI: 1.24–2.20), neutrophils (HR = 1.49, 1.13–1.97), and eosinophils (HR = 1.59, 1.18–2.14). Polygenic scores for blood cell traits are also differentially associated with 17 tumor immune microenvironment features in a subtype-specific manner, including signatures related to interferon signaling, PD-1 expression, and T-cell/Cytotoxic responses. Our findings highlight immune-mediated susceptibility mechanisms with potential disease management implications.https://doi.org/10.1038/s41467-025-55919-6 |
| spellingShingle | Linda Kachuri Geno A. Guerra Taishi Nakase George A. Wendt Helen M. Hansen Annette M. Molinaro Paige Bracci Lucie McCoy Terri Rice John K. Wiencke Jeanette E. Eckel-Passow Robert B. Jenkins Margaret Wrensch Stephen S. Francis Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival Nature Communications |
| title | Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival |
| title_full | Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival |
| title_fullStr | Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival |
| title_full_unstemmed | Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival |
| title_short | Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival |
| title_sort | genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival |
| url | https://doi.org/10.1038/s41467-025-55919-6 |
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