Dataset Information

Deciphering the 8q24.21 association for glioma.

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 × 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 × 10(-67)). Validation of the non-GBM association was shown in three additional datasets (625 non-GBM cases, 2412 controls; P = 1.41 × 10(-28)). In the pooled analysis, the odds ratio for low-grade glioma associated with rs55705857 was 4.3 (P = 2.31 × 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.

SUBMITTER: Enciso-Mora V

PROVIDER: S-EPMC3652416 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Deciphering the 8q24.21 association for glioma.

Enciso-Mora Victor V Hosking Fay J FJ Kinnersley Ben B Wang Yufei Y Shete Sanjay S Zelenika Diana D Broderick Peter P Idbaih Ahmed A Delattre Jean-Yves JY Hoang-Xuan Khe K Marie Yannick Y Di Stefano Anna Luisa AL Labussière Marianne M Dobbins Sara S Boisselier Blandine B Ciccarino Pietro P Rossetto Marta M Armstrong Georgina G Liu Yanhong Y Gousias Konstantinos K Schramm Johannes J Lau Ching C Hepworth Sarah J SJ Strauch Konstantin K Müller-Nurasyid Martina M Schreiber Stefan S Franke Andre A Moebus Susanne S Eisele Lewin L Forsti Asta A Hemminki Kari K Tomlinson Ian P IP Swerdlow Anthony A Lathrop Mark M Simon Matthias M Bondy Melissa M Sanson Marc M Houlston Richard S RS

Human molecular genetics 20130211 11

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 ...[more]

PMID: 23399484

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Project description:BACKGROUND:Several single nucleotide polymorphisms (SNPs), rs16892766 in the 8q23.3 region and rs6983267, rs10505477, rs7014346 and rs7837328 in the 8q24.21 region, have been identified by genome-wide association studies (GWAS) and a number of case-control studies to be closely associated with risk of colorectal cancer (CRC). In the present study, a meta-analysis was performed to confirm if these loci are risk factors for susceptibility to CRC, taking heterogeneity of population into consideration. METHODS:The whole literature search was conducted via database of MEDLINE and Embase, through which 33 articles with 49 studies (141,899 cases and 157,536 controls) were finally included in this meta-analysis to evaluate the association between the 5 polymorphisms and risk of CRC under allelic model. RESULTS:A meta-analysis of the pooled data showed that the G allele of rs6983267, the A allele of rs7014346, the T allele of rs10505477, the C allele of rs16892766 and the A allele of rs7837328 were associated with significantly increased risk of CRC under allelic model. Additionally, subgroup analyses of four SNPs (rs7837328 excluded) by ethnicity witnessed a notable association between the G allele of rs6983267 and increased risk of CRC among Caucasians, Asians and Africans. Furthermore, the C allele of rs16892766 was strongly linked with elevated risk of CRC among Caucasians and Africans. However, the A allele of rs7014346 and T allele of rs10505477 only heightened risk for CRC among Caucasians and showed no effects among Asians. CONCLUSION:In summary, rs6983267 is a risk factor for CRC among Caucasians, Asians and Africans; rs7014346 and rs10505477 are risky genetic polymorphisms only among Caucasians; rs16892766 is a hazardous element among populations with Caucasian and African ancestry; and rs7837328 could elevate the susceptibility to CRC in a multinational group. However, more potential factors related with CRC risk should be investigated in further studies.

Dataset Information

Deciphering the 8q24.21 association for glioma.

Publications

Deciphering the 8q24.21 association for glioma.

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