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

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. Genome-wide association study, Meningioma, Risk, Single-nucleotide polymorphism, Polygenic © The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuro-Oncology Oxford University Press

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Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.
ISSN
1522-8517
eISSN
1523-5866
D.O.I.
10.1093/neuonc/noy077
Publisher site
See Article on Publisher Site

Abstract

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. Genome-wide association study, Meningioma, Risk, Single-nucleotide polymorphism, Polygenic © The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Journal

Neuro-OncologyOxford University Press

Published: May 12, 2018

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