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Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma

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Harvard

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 2019, 'Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma' Cancer Research, bind 79, nr. 8, s. 2065-2071. https://doi.org/10.1158/0008-5472.CAN-18-2888

APA

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

CBE

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. 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

MLA

Vancouver

Atkins I, Kinnersley B, Ostrom QT, Labreche K, Il'yasova D, Armstrong GN o.a. 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

Author

Atkins, Isabelle ; Kinnersley, Ben ; Ostrom, Quinn T ; Labreche, Karim ; Il'yasova, Dora ; Armstrong, Georgina N ; Eckel-Passow, Jeanette E ; Schoemaker, Minouk J ; Nöthen, Markus M ; Barnholtz-Sloan, Jill S ; Swerdlow, Anthony J ; Simon, Matthias ; Rajaraman, Preetha ; Chanock, Stephen J ; Shildkraut, Joellen ; Bernstein, Jonine L ; Hoffmann, Per ; Jöckel, Karl-Heinz ; Lai, Rose K ; Claus, Elizabeth B ; Olson, Sara H ; Johansen, Christoffer ; Wrensch, Margaret R ; Melin, Beatrice ; Jenkins, Robert B ; Sanson, Marc ; Bondy, Melissa L ; Houlston, Richard S. / Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma. I: Cancer Research. 2019 ; Bind 79, Nr. 8. s. 2065-2071.

Bibtex

@article{da991a193bd84365a6380ef31f2a0d45,
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 = 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.",
author = "Isabelle Atkins and Ben Kinnersley and Ostrom, {Quinn T} and Karim Labreche and Dora Il'yasova and Armstrong, {Georgina N} and Eckel-Passow, {Jeanette E} and Schoemaker, {Minouk J} and N{\"o}then, {Markus M} and Barnholtz-Sloan, {Jill S} and Swerdlow, {Anthony J} and Matthias Simon and Preetha Rajaraman and Chanock, {Stephen J} and Joellen Shildkraut and Bernstein, {Jonine L} and Per Hoffmann and Karl-Heinz J{\"o}ckel and Lai, {Rose K} and Claus, {Elizabeth B} and Olson, {Sara H} and Christoffer Johansen and Wrensch, {Margaret R} and Beatrice Melin and Jenkins, {Robert B} and Marc Sanson and Bondy, {Melissa L} and Houlston, {Richard S}",
note = "{\circledC}2019 American Association for Cancer Research.",
year = "2019",
month = "4",
day = "15",
doi = "10.1158/0008-5472.CAN-18-2888",
language = "English",
volume = "79",
pages = "2065--2071",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research (A A C R)",
number = "8",

}

RIS

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 - Nöthen, 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 - Jöckel, 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 - ©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 = 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.

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 = 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.

U2 - 10.1158/0008-5472.CAN-18-2888

DO - 10.1158/0008-5472.CAN-18-2888

M3 - Journal article

VL - 79

SP - 2065

EP - 2071

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 8

ER -

ID: 57397689