Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors

Beatrice S. Melin (1) , Jill S. Barnholtz-Sloan (2) , Margaret R. Wrensch (3, 4) , Christoffer Johansen (5, 6) , Dora Il'Yasova (7, 8) , Ben Kinnersley (9) , Quinn T. Ostrom (2) , Karim Labreche (9, 10, 11, 12, 13) , Yanwen Chen (2) , Georgina Armstrong (14) , Yanhong Liu (14) , Jeanette E. Eckel-Passow (15) , Paul A. Decker (15) , Marianne Labussiere (9, 10, 11, 12, 13) , Ahmed Idbaih (9, 10, 11, 12, 13, 16) , Khe Hoang-Xuan (9, 10, 11, 12, 13, 16) , Anna-Luisa Di Stefano (9, 10, 11, 12, 13, 16) , Karima Mokhtari (9, 10, 11, 12, 13, 16) , Jean-Yves Delattre (9, 10, 11, 12, 13, 16) , Peter Broderick (9) , Pilar Galan Hercberg (17) , Konstantinos Gousias (18) , Johannes Schramm (18) , Minouk J. Schoemaker (9) , Sarah J. Fleming (19) , Stefan Herms (19) , Stefanie Heilmann (4) , Markus M. Noethen , Heinz-Erich Wichmann (20, 21) , Stefan Schreiber (22) , Anthony Swerdlow (9, 23) , Mark Lathrop (24, 25) , Matthias Simon (26) , Marc Sanson (9, 10, 11, 12, 13, 16) , Ulrika Andersson (1) , Preetha Rajaraman (27) , Stephen Chanock (27) , Martha Linet (27) , Zhaoming Wang (27) , Meredith Yeager (27) , John K. Wiencke (3, 4) , Helen Hansen (28) , Lucie Mccoy (28) , Terri Rice (28) , Matthew L. Kosel (15) , Hugues Sicotte (15) , Christopher I. Amos (29) , Jonine L. Bernstein (30) , Faith Davis (31) , Dan Lachance (32) , Ching Lau (33) , Ryan T. Merrell (34) , Joellen Shildkraut (35, 36) , Francis Ali-Osman (35, 37) , Siegal Sadetzki (38, 39) , Michael Scheurer (33) , Sanjay Shete (40) , Rose K. Lai (41) , Elizabeth B. Claus (42, 43) , Sara H. Olson (30) , Robert B. Jenkins (44) , Richard S. Houlston (9, 45) , Mélissa L. Bondy (46)

1 Department of Radiation Sciences [Umeå]
2 Case Comprehensive Cancer Center, School of Medicine
3 Department of Neurological Surgery, School of Medicine
4 Institute of Human Genetics
5 Institute of Cancer Epidemiology
6 Rigshospitalet [Copenhagen]
7 Duke Cancer Institute Durham, North Carolina, USA.
8 School of Public Health [Teheran]
9 Division of Genetics and Epidemiology
10 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute
11 CNRS - Centre National de la Recherche Scientifique
12 SU - Sorbonne Université
13 UPMC - Université Pierre et Marie Curie - Paris 6
14 Department of Medicine, Dan L. Duncan Comprehensive Cancer Center
15 Division of Biomedical Statistics anInformatics
16 CHU Pitié-Salpêtrière [AP-HP]
17 CRESS (U1153 / UMR_A_1125 / UMR_S_1153) - Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité
18 Department of Neurosurger
19 Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds
20 Institute of Epidemiology
21 Institute of Medical Statistics and Epidemiology Munich
22 1st Medical Department
23 Division of Breast Cancer Research London
24 Department of Human Genetics Montreal
25 Genome Québec
26 Department of Neurosurgery
27 Division of Cancer Epidemiology and Genetics
28 Department of Neurological Surgery, School of Medicine
29 Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth
30 Department of Epidemiology and Biostatistics
31 School of Public Health
32 Department of Neurology, Mayo Clinic Comprehensive Cancer Center
33 Department of Pediatrics, Dan L. Duncan Comprehensive Cancer Center
34 Department of Neurology Evanston, Illinois, USA.
35 Duke Cancer Institute Durham
36 Cancer Control and Prevention Program, Department of Community and Family Medicine Durham
37 Department of Surgery Durham, North
38 Cancer and Radiation Epidemiology Unit, Gertner Institute
39 Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine
40 Department of Biostatistics [Oslo]
41 Keck School of Medicine [Los Angeles]
42 School of Public Health New Haven
43 Department of Neurosurgery Boston
44 Department of Laboratory Medicine and Pathology
45 Division of Molecular Pathology
46 Department of Medicine, Dan L. Duncan Comprehensive Cancer Center Baylor Houston

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 x 10(-9), odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 x 10(-10), OR = 1.24), 16p13.3 (rs2562152; P = 1.93 x 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 x 10(-11), OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 x 10(-10), OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 x 10(-9), OR = 1.19), 1q44 (rs12076373; P = 2.63 x 10(-10), OR = 1.23), 2q33.3 (rs7572263; P = 2.18 x 10(-10), OR = 1.20), 3p14.1 (rs11706832; P = 7.66 x 10(-9), OR = 1.15), 10q24.33 (rs11598018; P = 3.39 x 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 x 10(-10), OR = 1.16), 14q12 (rs10131032; P = 5.07 x 10(-11), OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 x 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.

Domaines: Sciences du Vivant [q-bio]

Beatrice S. Melin, Jill S. Barnholtz-Sloan, Margaret R. Wrensch, Christoffer Johansen, Dora Il'Yasova, et al.. Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors. Nature Genetics, 2017, 49 (5), pp.789-794. ⟨10.1038/ng.3823⟩. ⟨hal-01602681⟩