TY - JOUR
T1 - Transcriptome-wide association study identifies new candidate susceptibility genes for glioma
AU - Atkins, Isabelle
AU - Kinnersley, Ben
AU - Ostrom, Quinn T.
AU - Labreche, Karim
AU - Il'yasova, Dora
AU - Armstrong, Georgina N.
AU - Eckel-Passow, Jeanette E.
AU - Schoemaker, Minouk J.
AU - Nothen, Markus M.
AU - Barnholtz-Sloan, Jill S.
AU - Swerdlow, Anthony J.
AU - Simon, Matthias
AU - Rajaraman, Preetha
AU - Chanock, Stephen J.
AU - Shildkraut, Joellen
AU - Bernstein, Jonine L.
AU - Hoffmann, Per
AU - Jockel, Karl Heinz
AU - Lai, Rose K.
AU - Claus, Elizabeth B.
AU - Olson, Sara H.
AU - Johansen, Christoffer
AU - Wrensch, Margaret R.
AU - Melin, Beatrice
AU - Jenkins, Robert B.
AU - Sanson, Marc
AU - Bondy, Melissa L.
AU - Houlston, Richard S.
PY - 2019
Y1 - 2019
N2 - 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 ¼ 4.43; P ¼ 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.
AB - 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 ¼ 4.43; P ¼ 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.
U2 - 10.1158/0008-5472.CAN-18-2888
DO - 10.1158/0008-5472.CAN-18-2888
M3 - Journal article
C2 - 30709929
AN - SCOPUS:85064463582
VL - 79
SP - 2065
EP - 2071
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 8
ER -