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Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma

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  • Isabelle Atkins
  • Ben Kinnersley
  • Quinn T Ostrom
  • Karim Labreche
  • Dora Il'yasova
  • Georgina N Armstrong
  • Jeanette E Eckel-Passow
  • Minouk J Schoemaker
  • Markus M Nöthen
  • Jill S Barnholtz-Sloan
  • Anthony J Swerdlow
  • Matthias Simon
  • Preetha Rajaraman
  • Stephen J Chanock
  • Joellen Shildkraut
  • Jonine L Bernstein
  • Per Hoffmann
  • Karl-Heinz Jöckel
  • Rose K Lai
  • Elizabeth B Claus
  • Sara H Olson
  • Christoffer Johansen
  • Margaret R Wrensch
  • Beatrice Melin
  • Robert B Jenkins
  • Marc Sanson
  • Melissa L Bondy
  • Richard S Houlston
Vis graf over relationer

Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility variants reside in noncoding regions and the causal genes underlying the associations are largely unknown. Here we performed a transcriptome-wide association study to search for novel risk loci and candidate causal genes at known GWAS loci using Genotype-Tissue Expression Project (GTEx) data to predict cis-predicted gene expression in relation to GBM and non-GBM risk in conjunction with GWAS summary statistics on 12,488 glioma cases (6,183 GBM and 5,820 non-GBM) and 18,169 controls. Imposing a Bonferroni-corrected significance level of P < 5.69 × 10-6, we identified 31 genes, including GALNT6 at 12q13.33, as a candidate novel risk locus for GBM (mean Z = 4.43; P = 5.68 × 10-6). GALNT6 resides at least 55 Mb away from any previously identified glioma risk variant, while all other 30 significantly associated genes were located within 1 Mb of known GWAS-identified loci and were not significant after conditioning on the known GWAS-identified variants. These data identify a novel locus (GALNT6 at 12q13.33) and 30 genes at 12 known glioma risk loci associated with glioma risk, providing further insights into glioma tumorigenesis. SIGNIFICANCE: This study identifies new genes associated with glioma risk, increasing understanding of how these tumors develop.

OriginalsprogEngelsk
TidsskriftCancer Research
Vol/bind79
Udgave nummer8
Sider (fra-til)2065-2071
Antal sider7
ISSN0008-5472
DOI
StatusUdgivet - 15 apr. 2019

Bibliografisk note

©2019 American Association for Cancer Research.

ID: 57397689