Genome-wide association analysis identifies a meningioma risk locus at 11p15.5
- Claus, Elizabeth B Department of Neurosurgery, Brigham and Women’s Hospital, Boston, Massachusetts, USA
- Cornish, Alex J ORCID Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
- Broderick, Peter Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
- Schildkraut, Joellen M Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA
- Dobbins, Sara E Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
- Holroyd, Amy Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
- Calvocoressi, Lisa School of Public Health, Yale University, New Haven, Connecticut, USA
- Lu, Lingeng School of Public Health, Yale University, New Haven, Connecticut, USA
- Hansen, Helen M Division of Neuroepidemiology, Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA
- Smirnov, Ivan Division of Neuroepidemiology, Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA
- Walsh, Kyle M Division of Neuroepidemiology, Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA
- Schramm, Johannes University of Bonn Medical School, Bonn, Germany
- Hoffmann, Per Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
- Nöthen, Markus M Institute of Human Genetics, University of Bonn School of Medicine and University Hospital Bonn, Bonn, Germany
- Jöckel, Karl-Heinz Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Swerdlow, Anthony Division of Breast Cancer Research, The Institute of Cancer Research, London, UK
- Larsen, Signe Benzon Unit of Survivorship, The Danish Cancer Society Research Center, Copenhagen, Denmark
- Johansen, Christoffer Unit of Survivorship, The Danish Cancer Society Research Center, Copenhagen, Denmark
- Simon, Matthias Department of Neurosurgery, Bethel Clinic, Bielefeld, Germany
- Bondy, Melissa Section of Epidemiology and Population Sciences, Department of Medicine and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA
- Wrensch, Margaret Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA
- Houlston, Richard S Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
- Wiemels, Joseph L Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
- 2018-5-12
Published in:
- Neuro-Oncology. - Oxford University Press (OUP). - 2018, vol. 20, no. 11, p. 1485-1493
English
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.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1093/neuonc/noy077
- ISSN 1522-8517
- Persistent URL
- https://sonar.ch/global/documents/5679
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