Transcriptome-wide association study identifies new candidate susceptibility genes for glioma Journal Article
| Authors: | Atkins, I.; Kinnersley, B.; Ostrom, Q. T.; Labreche, K.; Il'yasova, D.; Armstrong, G. N.; Eckel-Passow, J. E.; Schoemaker, M. J.; Nothen, M. M.; Barnholtz-Sloan, J. S.; Swerdlow, A. J.; Simon, M.; Rajaraman, P.; Chanock, S. J.; Shildkraut, J.; Bernstein, J. L.; Hoffmann, P.; Jockel, K. H.; Lai, R. K.; Claus, E. B.; Olson, S. H.; Johansen, C.; Wrensch, M. R.; Melin, B.; Jenkins, R. B.; Sanson, M.; Bondy, M. L.; Houlston, R. S. |
| Article Title: | Transcriptome-wide association study identifies new candidate susceptibility genes for glioma |
| 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 1⁄4 4.43; P 1⁄4 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. ©2019 American Association for Cancer Research. |
| Journal Title: | Cancer Research |
| Volume: | 79 |
| Issue: | 8 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2019-01-01 |
| Start Page: | 2065 |
| End Page: | 2071 |
| Language: | English |
| DOI: | 10.1158/0008-5472.Can-18-2888 |
| PROVIDER: | scopus |
| PUBMED: | 30709929 |
| PMCID: | PMC6522343 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2019 -- Source: Scopus |
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