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Genome-wide association analysis identifies a meningioma risk locus at 11p15.5
- Claus, Elizabeth B;
- Cornish, Alex J;
- Broderick, Peter;
- Schildkraut, Joellen M;
- Dobbins, Sara E;
- Holroyd, Amy;
- Calvocoressi, Lisa;
- Lu, Lingeng;
- Hansen, Helen M;
- Smirnov, Ivan;
- Walsh, Kyle M;
- Schramm, Johannes;
- Hoffmann, Per;
- Nöthen, Markus M;
- Jöckel, Karl-Heinz;
- Swerdlow, Anthony;
- Larsen, Signe Benzon;
- Johansen, Christoffer;
- Simon, Matthias;
- Bondy, Melissa;
- Wrensch, Margaret;
- Houlston, Richard S;
- Wiemels, Joseph L
Abstract
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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