Quantifying the heritability of glioma using genome-wide complex trait analysis.

Autor: Kinnersley B; Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK., Mitchell JS; Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK., Gousias K; Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Str. 25, 53105 Bonn, Germany., Schramm J; Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Str. 25, 53105 Bonn, Germany., Idbaih A; 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., Labussière M; Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, F-75013 Paris, France., Marie Y; Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, F-75013 Paris, France., Rahimian A; Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, F-75013 Paris, France.; Onconeurotek, F-75013 Paris, France., Wichmann HE; 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., Schreiber S; 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., Hoang-Xuan K; 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., Delattre JY; 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., Nöthen MM; Institute of Human Genetics, University of Bonn, Bonn, Germany., Mokhtari K; AP-HP, GH Pitié-Salpêtrière, Laboratoire de neuropathologie R Escourolle, F-75013 Paris, France., Lathrop M; Fondation Jean Dausset-CEPH, 27 Rue Juliette Dodu, 75010 Paris, France.; Génome Québec, Department of Human Genetics, McGill University, Montreal, Quebec, H3A 0G1, Canada., Bondy M; Department of Pediatrics, Division of Hematology-Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA., Simon M; Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Str. 25, 53105 Bonn, Germany., Sanson M; 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., Houlston RS; Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2015 Dec 02; Vol. 5, pp. 17267. Date of Electronic Publication: 2015 Dec 02.
DOI: 10.1038/srep17267
Abstrakt: 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.
Databáze: MEDLINE