Abstract
Previous genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of glioma. To identify new glioma susceptibility loci, we conducted a meta-analysis of four GWAS (totalling 4,147 cases and 7,435 controls), with imputation using 1000 Genomes and UK10K Project data as reference. After genotyping an additional 1,490 cases and 1,723 controls we identify new risk loci for glioblastoma (GBM) at 12q23.33 (rs3851634, near POLR3B, P=3.02 × 10−9) and non-GBM at 10q25.2 (rs11196067, near VTI1A, P=4.32 × 10−8), 11q23.2 (rs648044, near ZBTB16, P=6.26 × 10−11), 12q21.2 (rs12230172, P=7.53 × 10−11) and 15q24.2 (rs1801591, near ETFA, P=5.71 × 10−9). Our findings provide further insights into the genetic basis of the different glioma subtypes.
Highlights
Previous genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of glioma
Support for polygenic susceptibility to glioma has come from genome-wide association studies (GWASs) that have identified single-nucleotide polymorphisms (SNPs) at eight loci influencing glioma risk— 3q26.2, 5p15.33, 7p11.2, 8q24.21, 9p21.3, 11q23.3, 17p13.1 (TP53) and 20q13.33
To identify additional glioma susceptibility loci we conducted a pooled meta-analysis of four GWASs in populations of European ancestry, the UK-GWAS, the FrenchGWAS, the German-GWAS and the US-GWAS, that were genotyped using either Illumina HumanHap 317, 317 þ 240S, 370Duo, 550, 610 or 1M arrays (Supplementary Table 1)
Summary
Previous genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of glioma. To identify new glioma susceptibility loci, we conducted a meta-analysis of four GWAS (totalling 4,147 cases and 7,435 controls), with imputation using 1000 Genomes and UK10K Project data as reference. Direct evidence for inherited predisposition to glioma is provided by a number of rare inherited cancer syndromes, such as Turcot’s and Li–Fraumeni syndromes, and neurofibromatosis[4]. Even collectively, these diseases account for little of the twofold increased risk of glioma seen in first-degree relatives of glioma patients[5]. We report a meta-analysis of four GWASs totalling 4,147 cases and 7,435 controls to identify new glioma susceptibility loci, after imputation using the 1000 Genomes and the UK10K Project data as reference. Our findings provide further insights into the genetic basis of the different glioma subtypes
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