Language

English

Publication Date

1-1-2026

Journal

Neuro-Oncology Advances

DOI

10.1093/noajnl/vdag004

PMID

41869074

PMCID

PMC13000888

PubMedCentral® Posted Date

1-16-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Ependymoma is a malignancy of the neuroepithelium-derived ependyma that lines the spinal cord and ventricles of the brain, occurring most frequently in young children and older adults. Genetic susceptibility to ependymoma has proven difficult to assess due to disease rarity.

Methods: We performed genome-wide association studies (GWAS) of 478 ependymoma patients and 4,841 disease-free controls of European ancestry. Ependymoma patients consisted of 117 children (< 18 years old) with whole-genome sequencing (WGS), 142 children with genotyping, and 219 adults (≥18 years old) with genotyping. Genotyped samples were imputed using the 1,000 Genomes Project as the reference panel and underwent quality control filtering. The GWAS was performed separately by age group and technology (genotyped or WGS). GWAS variants were considered significant at P < 5 × 10-8.

Results: Among pediatric subjects with WGS data, we identified a significant intronic variant in EDIL3 (rs149378, P = 1.9 × 10-8) and a nearly significant intronic variant in LHX4 (rs79008224, P = 7.2 × 10-8). In pediatric subjects with genotyped data, two significant intronic variants were detected: FAM149A (rs6852180, P = 1.8 × 10-8) and CYS1 (rs61052588, P = 3.0 × 10-8). Additionally, an intergenic variant near C1orf94 (rs1404350, P = 1.2 × 10-14) was highly significant. In genotyped adult subjects, a single variant was observed in KCNQ3 (rs79089725, P = 2.0 × 10-8).

Conclusion: Our analysis represents one of the most extensive ependymoma-specific GWAS conducted to date. Several significant intronic variants were harbored in genes associated with cancer and neurological disease. Future studies are needed to investigate the role of these age-specific alterations in ependymoma pathogenesis.

Keywords

central nervous system tumor, ependymoma, genome-wide association study, germline, single nucleotide polymorphism

Published Open-Access

yes

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