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.
N1 - Funding Information:
I. Atkins was supported by a Wellcome Trust Summer Student bursary. In the UK, additional funding was provided by Cancer Research UK (C1298/A8362). The Glioma International Case-Control Consortium Study was supported by grants from the NIH, Bethesda, MD (R01CA139020, R01CA52689, P50097257, and P30CA125123). The UK Interphone Study was supported by the European Commission Fifth Framework Program "Quality of Life and Management of Living Resources" and the UK Mobile Telecommunications and Health Pro-gramme. The Mobile Manufacturers Forum and the GSM Association provided funding for the study through the scientifically independent International Union against Cancer (UICC). R code for power calculations was kindly provided by Lang Wu.
Funding Information:
I. Atkins was supported by a Wellcome Trust Summer Student bursary. In the UK, additional funding was provided by Cancer Research UK (C1298/A8362). The Glioma International Case-Control Consortium Study was supported by grants from the NIH, Bethesda, MD (R01CA139020, R01CA52689, P50097257, and P30CA125123). The UK Interphone Study was supported by the European Commission Fifth Framework Program "Quality of Life and Management of Living Resources" and the UK Mobile Telecommunications and Health Programme. The Mobile Manufacturers Forum and the GSM Association provided funding for the study through the scientifically independent International Union against Cancer (UICC). R code for power calculations was kindly provided by Lang Wu.
Publisher Copyright:
©2019 American Association for Cancer Research.
PY - 2019/4/15
Y1 - 2019/4/15
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.
UR - http://www.scopus.com/inward/record.url?scp=85064463582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064463582&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-18-2888
DO - 10.1158/0008-5472.CAN-18-2888
M3 - Article
C2 - 30709929
AN - SCOPUS:85064463582
SN - 0008-5472
VL - 79
SP - 2065
EP - 2071
JO - Cancer research
JF - Cancer research
IS - 8
ER -