A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation

Robert Brian Jenkins, Yuanyuan Xiao, Hugues Sicotte, Paul A. Decker, Thomas M. Kollmeyer, Helen M. Hansen, Matthew L. Kosel, Shichun Zheng, Kyle M. Walsh, Terri Rice, Paige Bracci, Lucie S. McCoy, Ivan Smirnov, Joseph S. Patoka, George Hsuang, Joe L. Wiemels, Tarik Tihan, Alexander R. Pico, Michael D. Prados, Susan M. ChangMitchel S. Berger, Alissa A. Caron, Stephanie R. Fink, Chandralekha Halder, Amanda L. Rynearson, Brooke L. Fridley, Jan Craig Buckner, Brian Patrick O'Neill, Caterina Giannini, Daniel H Lachance, John K. Wiencke, Jeanette E Eckel-Passow, Margaret R. Wrensch

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Variants at 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR and subsequent validation SNP genotyping, we identified seven low-frequency SNPs at 8q24.21 that were strongly associated with glioma risk (P = 1 × 10-25 to 1 × 10-14). The most strongly associated SNP, rs55705857, remained highly significant after individual adjustment for the other top six SNPs and two previously published SNPs. After stratifying by histological and tumor genetic subtype, the most significant associations of rs55705857 were with oligodendroglial tumors and gliomas with mutant IDH1 or IDH2 (odds ratio (OR) = 5.1, P = 1.1 × 10-31 and OR = 4.8, P = 6.6 × 10 -22, respectively). Strong associations were observed for astrocytomas with mutated IDH1 or IDH2 (grades 2-4) (OR = 5.16-6.66, P = 4.7 × 10-12 to 2.2 × 10-8) but not for astrocytomas with wild-type IDH1 and IDH2 (smallest P = 0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA.

Original languageEnglish (US)
Pages (from-to)1122-1125
Number of pages4
JournalNature Genetics
Volume44
Issue number10
DOIs
StatePublished - Oct 2012

Fingerprint

Astrocytoma
Single Nucleotide Polymorphism
Mutation
Glioma
Neoplasms
Odds Ratio
Conserved Sequence
MicroRNAs
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Genetics

Cite this

A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation. / Jenkins, Robert Brian; Xiao, Yuanyuan; Sicotte, Hugues; Decker, Paul A.; Kollmeyer, Thomas M.; Hansen, Helen M.; Kosel, Matthew L.; Zheng, Shichun; Walsh, Kyle M.; Rice, Terri; Bracci, Paige; McCoy, Lucie S.; Smirnov, Ivan; Patoka, Joseph S.; Hsuang, George; Wiemels, Joe L.; Tihan, Tarik; Pico, Alexander R.; Prados, Michael D.; Chang, Susan M.; Berger, Mitchel S.; Caron, Alissa A.; Fink, Stephanie R.; Halder, Chandralekha; Rynearson, Amanda L.; Fridley, Brooke L.; Buckner, Jan Craig; O'Neill, Brian Patrick; Giannini, Caterina; Lachance, Daniel H; Wiencke, John K.; Eckel-Passow, Jeanette E; Wrensch, Margaret R.

In: Nature Genetics, Vol. 44, No. 10, 10.2012, p. 1122-1125.

Research output: Contribution to journalArticle

Jenkins, RB, Xiao, Y, Sicotte, H, Decker, PA, Kollmeyer, TM, Hansen, HM, Kosel, ML, Zheng, S, Walsh, KM, Rice, T, Bracci, P, McCoy, LS, Smirnov, I, Patoka, JS, Hsuang, G, Wiemels, JL, Tihan, T, Pico, AR, Prados, MD, Chang, SM, Berger, MS, Caron, AA, Fink, SR, Halder, C, Rynearson, AL, Fridley, BL, Buckner, JC, O'Neill, BP, Giannini, C, Lachance, DH, Wiencke, JK, Eckel-Passow, JE & Wrensch, MR 2012, 'A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation', Nature Genetics, vol. 44, no. 10, pp. 1122-1125. https://doi.org/10.1038/ng.2388
Jenkins, Robert Brian ; Xiao, Yuanyuan ; Sicotte, Hugues ; Decker, Paul A. ; Kollmeyer, Thomas M. ; Hansen, Helen M. ; Kosel, Matthew L. ; Zheng, Shichun ; Walsh, Kyle M. ; Rice, Terri ; Bracci, Paige ; McCoy, Lucie S. ; Smirnov, Ivan ; Patoka, Joseph S. ; Hsuang, George ; Wiemels, Joe L. ; Tihan, Tarik ; Pico, Alexander R. ; Prados, Michael D. ; Chang, Susan M. ; Berger, Mitchel S. ; Caron, Alissa A. ; Fink, Stephanie R. ; Halder, Chandralekha ; Rynearson, Amanda L. ; Fridley, Brooke L. ; Buckner, Jan Craig ; O'Neill, Brian Patrick ; Giannini, Caterina ; Lachance, Daniel H ; Wiencke, John K. ; Eckel-Passow, Jeanette E ; Wrensch, Margaret R. / A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation. In: Nature Genetics. 2012 ; Vol. 44, No. 10. pp. 1122-1125.
@article{20724b4d523f403488c819d0d1a634aa,
title = "A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation",
abstract = "Variants at 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR and subsequent validation SNP genotyping, we identified seven low-frequency SNPs at 8q24.21 that were strongly associated with glioma risk (P = 1 × 10-25 to 1 × 10-14). The most strongly associated SNP, rs55705857, remained highly significant after individual adjustment for the other top six SNPs and two previously published SNPs. After stratifying by histological and tumor genetic subtype, the most significant associations of rs55705857 were with oligodendroglial tumors and gliomas with mutant IDH1 or IDH2 (odds ratio (OR) = 5.1, P = 1.1 × 10-31 and OR = 4.8, P = 6.6 × 10 -22, respectively). Strong associations were observed for astrocytomas with mutated IDH1 or IDH2 (grades 2-4) (OR = 5.16-6.66, P = 4.7 × 10-12 to 2.2 × 10-8) but not for astrocytomas with wild-type IDH1 and IDH2 (smallest P = 0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA.",
author = "Jenkins, {Robert Brian} and Yuanyuan Xiao and Hugues Sicotte and Decker, {Paul A.} and Kollmeyer, {Thomas M.} and Hansen, {Helen M.} and Kosel, {Matthew L.} and Shichun Zheng and Walsh, {Kyle M.} and Terri Rice and Paige Bracci and McCoy, {Lucie S.} and Ivan Smirnov and Patoka, {Joseph S.} and George Hsuang and Wiemels, {Joe L.} and Tarik Tihan and Pico, {Alexander R.} and Prados, {Michael D.} and Chang, {Susan M.} and Berger, {Mitchel S.} and Caron, {Alissa A.} and Fink, {Stephanie R.} and Chandralekha Halder and Rynearson, {Amanda L.} and Fridley, {Brooke L.} and Buckner, {Jan Craig} and O'Neill, {Brian Patrick} and Caterina Giannini and Lachance, {Daniel H} and Wiencke, {John K.} and Eckel-Passow, {Jeanette E} and Wrensch, {Margaret R.}",
year = "2012",
month = "10",
doi = "10.1038/ng.2388",
language = "English (US)",
volume = "44",
pages = "1122--1125",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation

AU - Jenkins, Robert Brian

AU - Xiao, Yuanyuan

AU - Sicotte, Hugues

AU - Decker, Paul A.

AU - Kollmeyer, Thomas M.

AU - Hansen, Helen M.

AU - Kosel, Matthew L.

AU - Zheng, Shichun

AU - Walsh, Kyle M.

AU - Rice, Terri

AU - Bracci, Paige

AU - McCoy, Lucie S.

AU - Smirnov, Ivan

AU - Patoka, Joseph S.

AU - Hsuang, George

AU - Wiemels, Joe L.

AU - Tihan, Tarik

AU - Pico, Alexander R.

AU - Prados, Michael D.

AU - Chang, Susan M.

AU - Berger, Mitchel S.

AU - Caron, Alissa A.

AU - Fink, Stephanie R.

AU - Halder, Chandralekha

AU - Rynearson, Amanda L.

AU - Fridley, Brooke L.

AU - Buckner, Jan Craig

AU - O'Neill, Brian Patrick

AU - Giannini, Caterina

AU - Lachance, Daniel H

AU - Wiencke, John K.

AU - Eckel-Passow, Jeanette E

AU - Wrensch, Margaret R.

PY - 2012/10

Y1 - 2012/10

N2 - Variants at 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR and subsequent validation SNP genotyping, we identified seven low-frequency SNPs at 8q24.21 that were strongly associated with glioma risk (P = 1 × 10-25 to 1 × 10-14). The most strongly associated SNP, rs55705857, remained highly significant after individual adjustment for the other top six SNPs and two previously published SNPs. After stratifying by histological and tumor genetic subtype, the most significant associations of rs55705857 were with oligodendroglial tumors and gliomas with mutant IDH1 or IDH2 (odds ratio (OR) = 5.1, P = 1.1 × 10-31 and OR = 4.8, P = 6.6 × 10 -22, respectively). Strong associations were observed for astrocytomas with mutated IDH1 or IDH2 (grades 2-4) (OR = 5.16-6.66, P = 4.7 × 10-12 to 2.2 × 10-8) but not for astrocytomas with wild-type IDH1 and IDH2 (smallest P = 0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA.

AB - Variants at 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR and subsequent validation SNP genotyping, we identified seven low-frequency SNPs at 8q24.21 that were strongly associated with glioma risk (P = 1 × 10-25 to 1 × 10-14). The most strongly associated SNP, rs55705857, remained highly significant after individual adjustment for the other top six SNPs and two previously published SNPs. After stratifying by histological and tumor genetic subtype, the most significant associations of rs55705857 were with oligodendroglial tumors and gliomas with mutant IDH1 or IDH2 (odds ratio (OR) = 5.1, P = 1.1 × 10-31 and OR = 4.8, P = 6.6 × 10 -22, respectively). Strong associations were observed for astrocytomas with mutated IDH1 or IDH2 (grades 2-4) (OR = 5.16-6.66, P = 4.7 × 10-12 to 2.2 × 10-8) but not for astrocytomas with wild-type IDH1 and IDH2 (smallest P = 0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA.

UR - http://www.scopus.com/inward/record.url?scp=84866932650&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866932650&partnerID=8YFLogxK

U2 - 10.1038/ng.2388

DO - 10.1038/ng.2388

M3 - Article

C2 - 22922872

AN - SCOPUS:84866932650

VL - 44

SP - 1122

EP - 1125

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 10

ER -