# Discovery of genetic susceptibility variants in pediatric and adult ependymoma

## TL;DR

This study identifies genetic variants linked to ependymoma, a rare brain tumor, in both children and adults.

## Contribution

The study reports novel genome-wide significant intronic and intergenic variants associated with pediatric and adult ependymoma.

## Key findings

- A significant intronic variant in EDIL3 and a nearly significant variant in LHX4 were found in pediatric whole-genome sequencing data.
- Two significant intronic variants in FAM149A and CYS1 were identified in genotyped pediatric data.
- A highly significant intergenic variant near C1orf94 and a significant variant in KCNQ3 were found in adult subjects.

## Abstract

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.

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.

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).

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.