Journal
HUMAN MOLECULAR GENETICS
Volume 22, Issue 11, Pages 2293-2302Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddt063
Keywords
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Funding
- Cancer Research UK [C1298/A8362]
- Wellcome Trust [076113, 085475]
- DJ Fielding Medical Research Trust
- Sir John Fisher Foundation
- European Union [QLK4-CT-1999-01563]
- International Union against Cancer (UICC)
- Mobile Manufacturers' Forum
- GSM Association
- Mobile Telecommunications and Health Research (MTHR) Programme
- Health and Safety Executive, Department of Health and Safety Executive
- UK Network Operators
- NIH [CA119215, 5R01 CA070917]
- American Brain Tumor Association
- National Brain Tumor Society
- Delegation a la Recherche Clinique [MUL03012]
- Association pour la Recherche sur les Tumeurs Cerebrales (ARTC)
- Institut National du Cancer(INCa) [PL046]
- French Ministry of Higher Education and Research
- Deutsche Forschungsgemeinschaft [Si552, Schr285]
- Deutsche Krebshilfe [70-2385-Wi2, 70-3163-Wi3, 10-6262]
- BONFOR
- German Federal Ministry of Education and Research (BMBF)
- Helmholtz Zentrum Munchen
- German Research Center for Environmental Health, Neuherberg
- German National Genome Research Network (NGFN)
- Munich Center of Health Sciences (MC Health)
- Cancer Research UK [16459] Funding Source: researchfish
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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.
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