Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma - Sorbonne Université Access content directly
Journal Articles Cancer Research Year : 2019

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

Quinn Ostrom
Richard Houlston

Abstract

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.

Dates and versions

hal-04555785 , version 1 (23-04-2024)

Identifiers

Cite

Isabelle Atkins, Ben Kinnersley, Quinn Ostrom, Karim Labreche, Dora Il'Yasova, et al.. Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma. Cancer Research, 2019, 79 (8), pp.2065-2071. ⟨10.1158/0008-5472.CAN-18-2888⟩. ⟨hal-04555785⟩
6 View
0 Download

Altmetric

Share

Gmail Facebook X LinkedIn More