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

Cancer research

Authors: 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

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 -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 < 5.69 × 10, we identified 31 genes, including at 12q13.33, as a candidate novel risk locus for GBM (mean = 4.43; = 5.68 × 10). 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 ( 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.

©2019 American Association for Cancer Research.

PMID: 30709929

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