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Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis

To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF<5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A>T, p.(Lys3326Ter)BRCA2 p.Lys332X variant, which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G>A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00010000750 Illumina HumanExome-12v1_A 2391
EGAD00010000752 Illumina HumanExome-12v1_A 899
EGAD00010000754 Illumina HumanExome-12v1_A 596
EGAD00010000756 Illumina HumanExome-12v1_A 699
EGAD00010000758 Illumina HumanExome-12v1_A 906
Publications Citations
Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis.
Eur J Hum Genet 24: 2016 717-724