Transcriptome-wide association study identifies new candidate susceptibility genes for glioma

Isabelle Atkins, Ben Kinnersley, Quinn T. Ostrom, Karim Labreche, Dora Il'yasova, Georgina N. Armstrong, Jeanette E Eckel-Passow, Minouk J. Schoemaker, Markus M. Nothen, Jill S. Barnholtz-Sloan, Anthony J. Swerdlow, Matthias Simon, Preetha Rajaraman, Stephen J. Chanock, Joellen Shildkraut, Jonine L. Bernstein, Per Hoffmann, Karl Heinz Jockel, Rose K. Lai, Elizabeth B. ClausSara H. Olson, Christoffer Johansen, Margaret R. Wrensch, Beatrice Melin, Robert Brian Jenkins, Marc Sanson, Melissa L. Bondy, Richard S. Houlston

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)2065-2071
Number of pages7
JournalCancer Research
Volume79
Issue number8
DOIs
StatePublished - Apr 15 2019

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Transcriptome
Glioma
Genome-Wide Association Study
Glioblastoma
Genes
Neoplasms
Carcinogenesis
Genotype
Gene Expression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Atkins, I., Kinnersley, B., Ostrom, Q. T., Labreche, K., Il'yasova, D., Armstrong, G. N., ... Houlston, R. S. (2019). Transcriptome-wide association study identifies new candidate susceptibility genes for glioma. Cancer Research, 79(8), 2065-2071. https://doi.org/10.1158/0008-5472.CAN-18-2888

Transcriptome-wide association study identifies new candidate susceptibility genes for glioma. / Atkins, Isabelle; Kinnersley, Ben; Ostrom, Quinn T.; Labreche, Karim; Il'yasova, Dora; Armstrong, Georgina N.; Eckel-Passow, Jeanette E; Schoemaker, Minouk J.; Nothen, Markus M.; Barnholtz-Sloan, Jill S.; Swerdlow, Anthony J.; Simon, Matthias; Rajaraman, Preetha; Chanock, Stephen J.; Shildkraut, Joellen; Bernstein, Jonine L.; Hoffmann, Per; Jockel, Karl Heinz; Lai, Rose K.; Claus, Elizabeth B.; Olson, Sara H.; Johansen, Christoffer; Wrensch, Margaret R.; Melin, Beatrice; Jenkins, Robert Brian; Sanson, Marc; Bondy, Melissa L.; Houlston, Richard S.

In: Cancer Research, Vol. 79, No. 8, 15.04.2019, p. 2065-2071.

Research output: Contribution to journalArticle

Atkins, I, Kinnersley, B, Ostrom, QT, Labreche, K, Il'yasova, D, Armstrong, GN, Eckel-Passow, JE, Schoemaker, MJ, Nothen, MM, Barnholtz-Sloan, JS, Swerdlow, AJ, Simon, M, Rajaraman, P, Chanock, SJ, Shildkraut, J, Bernstein, JL, Hoffmann, P, Jockel, KH, Lai, RK, Claus, EB, Olson, SH, Johansen, C, Wrensch, MR, Melin, B, Jenkins, RB, Sanson, M, Bondy, ML & Houlston, RS 2019, 'Transcriptome-wide association study identifies new candidate susceptibility genes for glioma', Cancer Research, vol. 79, no. 8, pp. 2065-2071. https://doi.org/10.1158/0008-5472.CAN-18-2888
Atkins I, Kinnersley B, Ostrom QT, Labreche K, Il'yasova D, Armstrong GN et al. Transcriptome-wide association study identifies new candidate susceptibility genes for glioma. Cancer Research. 2019 Apr 15;79(8):2065-2071. https://doi.org/10.1158/0008-5472.CAN-18-2888
Atkins, Isabelle ; Kinnersley, Ben ; Ostrom, Quinn T. ; Labreche, Karim ; Il'yasova, Dora ; Armstrong, Georgina N. ; Eckel-Passow, Jeanette E ; Schoemaker, Minouk J. ; Nothen, Markus M. ; Barnholtz-Sloan, Jill S. ; Swerdlow, Anthony J. ; Simon, Matthias ; Rajaraman, Preetha ; Chanock, Stephen J. ; Shildkraut, Joellen ; Bernstein, Jonine L. ; Hoffmann, Per ; Jockel, Karl Heinz ; Lai, Rose K. ; Claus, Elizabeth B. ; Olson, Sara H. ; Johansen, Christoffer ; Wrensch, Margaret R. ; Melin, Beatrice ; Jenkins, Robert Brian ; Sanson, Marc ; Bondy, Melissa L. ; Houlston, Richard S. / Transcriptome-wide association study identifies new candidate susceptibility genes for glioma. In: Cancer Research. 2019 ; Vol. 79, No. 8. pp. 2065-2071.
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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 Brian

AU - Sanson, Marc

AU - Bondy, Melissa L.

AU - Houlston, Richard S.

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