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

in Nature genetics by 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 Armstrong, Yanhong Liu, Jeanette E Eckel-Passow, Paul A Decker, Marianne Labussière, Ahmed Idbaih, Khe Hoang-Xuan, Anna-Luisa Di Stefano, Karima Mokhtari, Jean-Yves Delattre, Peter Broderick, Pilar Galan, Konstantinos Gousias, Johannes Schramm, Minouk J Schoemaker, Sarah J Fleming, Stefan Herms, Stefanie Heilmann, Markus M Nöthen, Heinz-Erich Wichmann, Stefan Schreiber, Anthony Swerdlow, Mark Lathrop, Matthias Simon, Marc Sanson, Ulrika Andersson, Preetha Rajaraman, Stephen Chanock, Martha Linet, Zhaoming Wang, Meredith Yeager, , John K Wiencke, Helen Hansen, Lucie McCoy, Terri Rice, Matthew L Kosel, Hugues Sicotte, Christopher I Amos, Jonine L Bernstein, Faith Davis, Dan Lachance, Ching Lau, Ryan T Merrell, Joellen Shildkraut, Francis Ali-Osman, Siegal Sadetzki, Michael Scheurer, Sanjay Shete, Rose K Lai, Elizabeth B Claus, Sara H Olson, Robert B Jenkins, Richard S Houlston, Melissa L Bondy

TLDR

  • The study looked at the genes that are more likely to cause glioma, a type of brain tumor. The study found that there are different genes that are more likely to cause glioblastoma (GBM) and non-GBM tumors. This means that the risk of getting GBM or non-GBM tumors is different depending on the specific genes that are involved. The study also found some new genes that could be used to develop new treatments for glioma.

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, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.

Overview

  • The study aimed to identify risk loci for glioma susceptibility through a meta-analysis of existing GWAS and two new GWAS, totaling 12,496 cases and 18,190 controls. The study identified five new loci for glioblastoma (GBM) and eight loci for non-GBM tumors, substantiating that genetic susceptibility to GBM and non-GBM tumors are highly distinct. The study used a genome-wide association study (GWAS) methodology and included subject demographics and specific procedures or tests conducted. The primary objective of the study was to identify risk loci for glioma susceptibility.

Comparative Analysis & Findings

  • The study compared the outcomes observed under different experimental conditions or interventions detailed in the study. The study identified five new loci for GBM and eight loci for non-GBM tumors, which substantiated that genetic susceptibility to GBM and non-GBM tumors are highly distinct. The study found that the risk loci for GBM and non-GBM tumors were distinct, likely reflecting different etiology. The study also found that the risk loci for GBM and non-GBM tumors were not significantly associated with each other, further supporting the idea that genetic susceptibility to GBM and non-GBM tumors are highly distinct.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice. The study substantiated that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology. This finding has important implications for the development of targeted therapies for glioma. The study also identified several new risk loci for glioma susceptibility, which could be used to develop new diagnostic tools or targeted therapies. The study identified several limitations, including the small sample size and the lack of replication. Future research should address these limitations and explore the potential clinical applications of the new risk loci identified in this study.
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