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

Beatrice S Melin, Jill S Barnholtz-Sloan, Margaret R. Wrensch, Christoffer Johansen, Dora Il'yasova, Ben Kinnersley, Quinn T Ostrom, Karim Labreche, Yanwen Chen, Georgina N Armstrong, Yanhong Liu, Jeanette Eckel-Passow, Paul A Decker, Marianne Labussière, Ahmed Idbaih, Khe Hoang-Xuan, Anna-Luisa Di Stefano, Karima Mokhtari, Jean-Yves Delattre, Peter BroderickPilar Galan, Konstantinos Gousias, Johannes Schramm, Minouk J Schoemaker, Sarah J Fleming, Stefan Herms, Stefanie Heilmann-Heimbach, Markus M Nöthen, Heinz-Erich Wichmann, Stefan Schreiber, Anthony Swerdlow, Mark Lathrop, Matthias Simon, Marc Sanson, Ulrika Andersson, Preetha Rajaraman, Stephen Chanock, Martha S Linet, Zhaoming Wang, Meredith Yeager, GliomaScan Consortium, John K Wiencke, Helen Hansen, Lucie S. Mccoy, Terri Rice, Matthew L Kosel, Hugues Sicotte, Christopher I Amos, Jonine L Bernstein, Faith G Davis, Dan Lachance

115 Citations (Scopus)

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.

Original languageEnglish
JournalNature Genetics
Volume49
Issue number5
Pages (from-to)789-794
Number of pages6
ISSN1061-4036
DOIs
Publication statusPublished - 1 May 2017

Keywords

  • Journal Article

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