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

Author:

Claus Elizabeth B12,Cornish Alex J3ORCID,Broderick Peter3,Schildkraut Joellen M4,Dobbins Sara E3,Holroyd Amy13,Calvocoressi Lisa11,Lu Lingeng11,Hansen Helen M15,Smirnov Ivan15,Walsh Kyle M15,Schramm Johannes16,Hoffmann Per178,Nöthen Markus M189,Jöckel Karl-Heinz110,Swerdlow Anthony311,Larsen Signe Benzon12,Johansen Christoffer12,Simon Matthias613,Bondy Melissa14,Wrensch Margaret515,Houlston Richard S3,Wiemels Joseph L51516

Affiliation:

1. School of Public Health, Yale University, New Haven, Connecticut, USA

2. Department of Neurosurgery, Brigham and Women’s Hospital, Boston, Massachusetts, USA

3. Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK

4. Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA

5. Division of Neuroepidemiology, Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA

6. University of Bonn Medical School, Bonn, Germany

7. Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland

8. Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany

9. Institute of Human Genetics, University of Bonn School of Medicine and University Hospital Bonn, Bonn, Germany

10. Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

11. Division of Breast Cancer Research, The Institute of Cancer Research, London, UK

12. Unit of Survivorship, The Danish Cancer Society Research Center, Copenhagen, Denmark

13. Department of Neurosurgery, Bethel Clinic, Bielefeld, Germany

14. Section of Epidemiology and Population Sciences, Department of Medicine and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA

15. Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA

16. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA

Abstract

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.

Funder

Cancer Research UK

Bobby Moore Fund

European Union Fifth Framework Program

Union for International Cancer Control

Deutsche Forschungsgemeinschaft

Deutsche Krebshilfe

BONFOR

Heinz Nixdorf Foundation

German Ministry of Education and Science and the German Research Council

Brain Science Foundation

Meningioma Mommas

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Neurology (clinical),Oncology

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