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Deciphering the 8q24.21 association for glioma

Enciso-Mora, Victor; Hosking, Fay J.; Kinnersley, Ben; Wang, Yufei; Shete, Sanjay; Zelenika, Diana; Broderick, Peter; Idbaih, Ahmed; Delattre, Jean-Yves and Hoang-Xuan, Khe, et al. (2013) In Human Molecular Genetics 22(11). p.2293-2302
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... (More)
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. (Less)
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@article{75e8f7e5-e8f9-48e9-83aa-ba1a139de0ec,
  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.},
  author       = {Enciso-Mora, Victor and Hosking, Fay J. and Kinnersley, Ben and Wang, Yufei and Shete, Sanjay and Zelenika, Diana and Broderick, Peter and Idbaih, Ahmed and Delattre, Jean-Yves and Hoang-Xuan, Khe and Marie, Yannick and Di Stefano, Anna Luisa and Labussiere, Marianne and Dobbins, Sara and Boisselier, Blandine and Ciccarino, Pietro and Rossetto, Marta and Armstrong, Georgina and Liu, Yanhong and Gousias, Konstantinos and Schramm, Johannes and Lau, Ching and Hepworth, Sarah J. and Strauch, Konstantin and Mueller-Nurasyid, Martina and Schreiber, Stefan and Franke, Andre and Moebus, Susanne and Eisele, Lewin and Försti, Asta and Hemminki, Kari and Tomlinson, Ian P. and Swerdlow, Anthony and Lathrop, Mark and Simon, Matthias and Bondy, Melissa and Sanson, Marc and Houlston, Richard S.},
  issn         = {0964-6906},
  language     = {eng},
  number       = {11},
  pages        = {2293--2302},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Deciphering the 8q24.21 association for glioma},
  url          = {http://dx.doi.org/10.1093/hmg/ddt063},
  volume       = {22},
  year         = {2013},
}