Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma.
Date
2019-04-15Author
Atkins, I
Kinnersley, B
Ostrom, QT
Labreche, K
Il'yasova, D
Armstrong, GN
Eckel-Passow, JE
Schoemaker, MJ
Nöthen, MM
Barnholtz-Sloan, JS
Swerdlow, AJ
Simon, M
Rajaraman, P
Chanock, SJ
Shildkraut, J
Bernstein, JL
Hoffmann, P
Jöckel, K-H
Lai, RK
Claus, EB
Olson, SH
Johansen, C
Wrensch, MR
Melin, B
Jenkins, RB
Sanson, M
Bondy, ML
Houlston, RS
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Glioma
Genetic Predisposition to Disease
Prognosis
Case-Control Studies
Gene Expression Regulation, Neoplastic
Genotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Genome-Wide Association Study
Transcriptome
Biomarkers, Tumor
Research team
Aetiological Epidemiology
Cancer Genomics
Language
eng
Date accepted
2019-01-24
License start date
2019-04
Citation
Cancer research, 2019, 79 (8), pp. 2065 - 2071
Publisher
AMER ASSOC CANCER RESEARCH