Genome-wide association analysis identifies a meningioma risk locus at 11p15.5.
Background: Meningiomas 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 2 GWAS, imputed using a merged reference panel from the 1000 Genomes Project and UK10K data, with validation in 2 independent sample series totaling 2138 cases and 12081 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.
Claus, EB; Cornish, AJ; Broderick, P; Schildkraut, JM; Dobbins, SE; Holroyd, A; Calvocoressi, L; Lu, L; Hansen, HM; Smirnov, I; Walsh, KM; Schramm, J; Hoffmann, P; Nöthen, MM; Jöckel, K-H; Swerdlow, A; Larsen, SB; Johansen, C; Simon, M; Bondy, M; Wrensch, M; Houlston, RS; Wiemels, JL
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