ArticleFrontiers in immunology2026
Imaging-mediated genetic effects link brain microstructure, metabolic profiles, and regional transcription to glioma susceptibility.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: This study aimed to systematically characterize genetically links and Mediation mechanism between glioma susceptibility and brain microstructure, cross-compartment metabolic profiles, and region-specific gene expression, followed by functional validation. Methods: Using GWAS data from 12,488 glioma cases and 18,169 controls, we performed two-sample MR (TSMR) and summary data-based MR (SMR) analyses. We evaluated 587 brain imaging-derived phenotypes (IDPs) from diffusion and structural MRI; levels of 962 brain tissue metabolites, 440 cerebrospinal fluid (CSF) metabolites, and 1,400 plasma metabolites; and eQTL based gene expression across 13 brain regions. A two-step MR design was employed for mediation analysis, and the key gene identified, Results: TSMR identified 6 IDPs significantly associated with all glioma subtypes. Specifically, elevated intracellular volume fraction (ICVF) in the corpus callosum and cingulum increased risk, while increased mean diffusivity (MD) in the posterior limb of the right internal capsule was protective. Integrated SMR and TSMR revealed that elevated Conclusion: This study provides robust multi-layered evidence for the causal roles of white matter microstructural abnormalities, metabolic dysregulation, and regional gene expression in glioma development. These findings offer novel genetic insights and potential therapeutic targets for precision medicine in glioma.
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