Kinnersley Ben, Labussière Marianne, Holroyd Amy, Di Stefano Anna-Luisa, Broderick Peter, Vijayakrishnan Jayaram, Mokhtari Karima, Delattre Jean-Yves, Gousias Konstantinos, Schramm Johannes, Schoemaker Minouk J, Fleming Sarah J, Herms Stefan, Heilmann Stefanie, Schreiber Stefan, Wichmann Heinz-Erich, Nöthen Markus M, Swerdlow Anthony, Lathrop Mark, Simon Matthias, Bondy Melissa, Sanson Marc, Houlston Richard S
Division of Genetics and Epidemiology, The Institute of Cancer Research, London SM2 5NG, UK.
Sorbonne Universités UPMC Univ Paris 06, INSERM CNRS, U1127, UMR 7225, ICM, F-75013 Paris, France.
Nat Commun. 2015 Oct 1;6:8559. doi: 10.1038/ncomms9559.
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.
以往的全基因组关联研究（GWAS）表明，常见的基因变异会导致胶质瘤的遗传易感性。为了确定新的胶质瘤易感位点，我们对四项GWAS进行了荟萃分析（共4147例病例和7435例对照），并以千人基因组计划和英国十万人基因组计划的数据作为参考进行基因填充。在对另外1490例病例和1723例对照进行基因分型后，我们在12q23.33（rs3851634，靠近POLR3B，P = 3.02×10^(-9)）发现了胶质母细胞瘤（GBM）的新风险位点，在10q25.2（rs11196067，靠近VTI1A，P = 4.32×10^(-8)）、11q23.2（rs648044，靠近ZBTB16，P = 6.26×10^(-11)）、12q21.2（rs12230172，P = 7.53×10^(-11)）和15q24.2（rs1801591，靠近ETFA，P = 5.71×10^(-9)）发现了非GBM的新风险位点。我们的研究结果为不同胶质瘤亚型的遗传基础提供了进一步的见解。
