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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 × 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.

Deciphering the 8q24.21 association for glioma