Genome-wide association analysis identifies a meningioma risk locus at 11p15.5

Abstract

BACKGROUND

Meningioma are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31.

METHODS

To identify a susceptibility locus for meningioma, we conducted a meta-analysis of two GWAS, imputed using a merged reference panel of 1,000 Genomes and UK10K data, with validation in two independent sample series totaling 2,138 cases and 12,081 controls.

RESULTS

We identified a new susceptibility locus for meningioma at 11p15.5 (rs2686876, odds ratio = 1.44, P = 9.86 × 10^-9). A number of genes localize to the region of linkage disequilibrium encompassing rs2686876, including RIC8A, which plays a central role in the development of neural crest-derived structures, such as the meninges.

CONCLUSIONS

This finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma.