title: Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.
abstract: Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10-9, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10-10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10-11, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10-10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10-9, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10-10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10-10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10-9, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10-10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10-11, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10-9, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
authors.affiliation: Department of Radiation Sciences, Umeå University, Umeå, Sweden.
authors.forename: Beatrice S
authors.initials: BS
authors.lastname: Melin
authors.affiliation: Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Jill S
authors.initials: JS
authors.lastname: Barnholtz-Sloan
authors.affiliation: Department of Neurological Surgery, School of Medicine, University of California, San Francisco, San Francisco, California, USA.|Institute of Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wrensch
authors.affiliation: Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark and Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Johansen
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Georgia State University, Atlanta, Georgia, USA.|Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.|Cancer Control and Prevention Program, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Dora
authors.initials: D
authors.lastname: Il'yasova
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Ben
authors.identifier: http://orcid.org/0000-0003-1783-6296
authors.initials: B
authors.lastname: Kinnersley
authors.affiliation: Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Quinn T
authors.initials: QT
authors.lastname: Ostrom
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.|Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, Paris, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Labreche
authors.affiliation: Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Georgina
authors.initials: G
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authors.affiliation: Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Yanhong
authors.initials: Y
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authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Eckel-Passow
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Decker
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, Paris, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Labussière
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, Paris, France.|AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, Paris, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Idbaih
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, Paris, France.|AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, Paris, France.
authors.forename: Khe
authors.initials: K
authors.lastname: Hoang-Xuan
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, Paris, France.|AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, Paris, France.
authors.forename: Anna-Luisa
authors.identifier: http://orcid.org/0000-0003-1746-0647
authors.initials: AL
authors.lastname: Di Stefano
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, Paris, France.|AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, Paris, France.
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, Paris, France.|AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Peter
authors.identifier: http://orcid.org/0000-0002-8348-5829
authors.initials: P
authors.lastname: Broderick
authors.affiliation: Université Paris 13 Sorbonne Paris Cité, INSERM U557, INRA U1125, CNAM, Paris, France.
authors.forename: Pilar
authors.initials: P
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authors.affiliation: Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany.
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authors.affiliation: Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schramm
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Minouk J
authors.initials: MJ
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authors.affiliation: Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
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authors.initials: SJ
authors.lastname: Fleming
authors.affiliation: Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
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authors.initials: S
authors.lastname: Herms
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
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authors.initials: S
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authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
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authors.affiliation: Helmholtz Center Munich, Institute of Epidemiology I, Munich, Germany.|Institute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians University, Munich, Germany.|Institute of Medical Statistics and Epidemiology, Technical University Munich, Munich, Germany.
authors.forename: Heinz-Erich
authors.initials: HE
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authors.affiliation: 1st Medical Department, University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.
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authors.initials: S
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authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.|Division of Breast Cancer Research, Institute of Cancer Research, London, UK.
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authors.initials: A
authors.lastname: Swerdlow
authors.affiliation: Génome Québec, Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
authors.forename: Mark
authors.initials: M
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authors.affiliation: Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany.
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authors.initials: M
authors.lastname: Simon
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, Paris, France.|AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.affiliation: Department of Radiation Sciences, Umeå University, Umeå, Sweden.
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authors.initials: U
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Preetha
authors.identifier: http://orcid.org/0000-0001-6649-999X
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Meredith
authors.initials: M
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authors.affiliation: Department of Neurological Surgery, School of Medicine, University of California, San Francisco, San Francisco, California, USA.|Institute of Human Genetics, University of California, San Francisco, San Francisco, California, USA.
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authors.initials: JK
authors.lastname: Wiencke
authors.affiliation: Department of Neurological Surgery, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
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authors.initials: H
authors.lastname: Hansen
authors.affiliation: Department of Neurological Surgery, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
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authors.lastname: McCoy
authors.affiliation: Department of Neurological Surgery, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
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authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
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authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
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authors.affiliation: Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
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authors.initials: CI
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authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
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authors.initials: JL
authors.lastname: Bernstein
authors.affiliation: School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
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authors.initials: F
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authors.affiliation: Department of Neurology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, USA.
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authors.initials: J
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authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.|Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
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authors.initials: F
authors.lastname: Ali-Osman
authors.affiliation: Cancer and Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel.|Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Siegal
authors.initials: S
authors.lastname: Sadetzki
authors.affiliation: Department of Pediatrics, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
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authors.initials: M
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authors.affiliation: Department of Biostatistics, University of Texas Maryland Anderson Cancer Center, Houston, Texas, USA.
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authors.affiliation: Departments of Neurology and Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Rose K
authors.initials: RK
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authors.affiliation: School of Public Health, Yale University, New Haven, Connecticut, USA.|Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Elizabeth B
authors.initials: EB
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authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
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authors.initials: SH
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authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, USA.
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authors.initials: RB
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authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.|Division of Molecular Pathology, Institute of Cancer Research, London, UK.
authors.forename: Richard S
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authors.affiliation: Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
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mesh_terms: D006801:Humans; D000483:Alleles; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D005909:Glioblastoma / Q000145:classification / Q000235:genetics; D005910:Glioma / Q000145:classification / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics