title: Quantifying the heritability of glioma using genome-wide complex trait analysis.
abstract: Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) influencing glioma risk. While these SNPs only explain a small proportion of the genetic risk it is unclear how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we applied Genome-Wide Complex Trait Analysis (GCTA) to three GWAS datasets totalling 3,373 cases and 4,571 controls and performed a meta-analysis to estimate the heritability of glioma. Our results identify heritability estimates of 25% (95% CI: 20-31%, P = 1.15 × 10(-17)) for all forms of glioma - 26% (95% CI: 17-35%, P = 1.05 × 10(-8)) for glioblastoma multiforme (GBM) and 25% (95% CI: 17-32%, P = 1.26 × 10(-10)) for non-GBM tumors. This is a substantial increase from the genetic variance identified by the currently identified GWAS risk loci (~6% of common heritability), indicating that most of the heritable risk attributable to common genetic variants remains to be identified.
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Kinnersley
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Mitchell
authors.affiliation: Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Gousias
authors.affiliation: Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schramm
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, F-75013 Paris, France.|AP-HP, GH Pitié-Salpêtrière, Service de Neurologie Mazarin, 47 bld de l'Hôpital, 75651 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, F-75013 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, F-75013 Paris, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Marie
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, F-75013 Paris, France.|Onconeurotek, F-75013 Paris, France.
authors.forename: Amithys
authors.initials: A
authors.lastname: Rahimian
authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.|Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Geschwister-Scholl-Platz 1, 80539 Munich, Germany.|Institute of Medical Statistics and Epidemiology, Technical University Munich, Germany.
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.affiliation: 1st Medical Department, University Clinic Schleswig-Holstein, Campus Kiel, House 6, Arnold-Heller-Str. 3, 24105 Kiel, Germany.|Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Arnold-Heller-Straβe 3, 24105 Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, F-75013 Paris, France.|AP-HP, GH Pitié-Salpêtrière, Service de Neurologie Mazarin, 47 bld de l'Hôpital, 75651 Paris, France.|Onconeurotek, F-75013 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, F-75013 Paris, France.|AP-HP, GH Pitié-Salpêtrière, Service de Neurologie Mazarin, 47 bld de l'Hôpital, 75651 Paris, France.|Onconeurotek, F-75013 Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: AP-HP, GH Pitié-Salpêtrière, Laboratoire de neuropathologie R Escourolle, F-75013 Paris, France.
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.affiliation: Fondation Jean Dausset-CEPH, 27 Rue Juliette Dodu, 75010 Paris, France.|Génome Québec, Department of Human Genetics, McGill University, Montreal, Quebec, H3A 0G1, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.affiliation: Department of Pediatrics, Division of Hematology-Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Bondy
authors.affiliation: Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Simon
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, F-75013 Paris, France.|AP-HP, GH Pitié-Salpêtrière, Service de Neurologie Mazarin, 47 bld de l'Hôpital, 75651 Paris, France.|Onconeurotek, F-75013 Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D055106:Genome-Wide Association Study; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D012189:Retrospective Studies