Deciphering the 8q24.21 association for glioma

Research output: Contribution to journalArticle

Abstract

We have previously identified tagSNPs at 8q24.21 influencing glioma risk. We have sought to fine-map the location of the functional basis of this association using data from four genome-wide association studies, comprising a total of 4147 glioma cases and 7435 controls. To improve marker density across the 700 kb region, we imputed genotypes using 1000 Genomes Project data and high-coverage sequencing data generated on 253 individuals. Analysis revealed an imputed low-frequency SNP rs55705857 (P = 2.24 x 10(-38)) which was sufficient to fully capture the 8q24.21 association. Analysis by glioma subtype showed the association with rs55705857 confined to non-glioblastoma multiforme (non-GBM) tumours (P = 1.07 x 10(-67)). Validation of the non-GBM association was shown in three additional datasets (625 non-GBM cases, 2412 controls; P = 1.41 x 10(-28)). In the pooled analysis, the odds ratio for low-grade glioma associated with rs55705857 was 4.3 (P = 2.31 x 10(-94)). rs55705857 maps to a highly evolutionarily conserved sequence within the long non-coding RNA CCDC26 raising the possibility of direct functionality. These data provide additional insights into the aetiological basis of glioma development.

Details

Authors
  • Victor Enciso-Mora
  • Fay J. Hosking
  • Ben Kinnersley
  • Yufei Wang
  • Sanjay Shete
  • Diana Zelenika
  • Peter Broderick
  • Ahmed Idbaih
  • Jean-Yves Delattre
  • Khe Hoang-Xuan
  • Yannick Marie
  • Anna Luisa Di Stefano
  • Marianne Labussiere
  • Sara Dobbins
  • Blandine Boisselier
  • Pietro Ciccarino
  • Marta Rossetto
  • Georgina Armstrong
  • Yanhong Liu
  • Konstantinos Gousias
  • Johannes Schramm
  • Ching Lau
  • Sarah J. Hepworth
  • Konstantin Strauch
  • Martina Mueller-Nurasyid
  • Stefan Schreiber
  • Andre Franke
  • Susanne Moebus
  • Lewin Eisele
  • Ian P. Tomlinson
  • Anthony Swerdlow
  • Mark Lathrop
  • Matthias Simon
  • Melissa Bondy
  • Marc Sanson
  • Richard S. Houlston
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Pages (from-to)2293-2302
JournalHuman Molecular Genetics
Volume22
Issue number11
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes