近期的测序研究揭示了10%的儿童胶质瘤是由罕见的生殖细胞突变引起的，然而常见变异的作用尚未确定，迄今尚未确定儿童中枢神经系统肿瘤的基因组范围内的显著风险位点。对三个人口基因组关联研究的荟萃分析（包括4,069名胶质瘤患儿和8,778名不同遗传祖先的对照者）。独立的病例对照组进行了复制。进行定量性状位点分析和转录组广泛关联研究，以评估与18,628个基因中的脑组织表达可能的关联。CDKN2B-AS1在9p21.3的常见变异与儿童中最常见的胶质瘤亚型（星形胶质细胞瘤）严格相关（rs573687，p值6.974e-10，OR 1.273，CI95 1.179-1.374）。这个关联是由低级星形胶质细胞瘤驱动的（p值3.815e-9），并在所有6种遗传祖先中表现出单向效应。对于总体胶质瘤而言，相关性达到了基因组范围内的显著水平（rs3731239，p值5.411e-8），而高级别肿瘤则没有显著的关联。预测CDKN2B脑组织表达下降与星形胶质细胞瘤严格相关（p值8.090e-8）。在这个基于人群的GWAS荟萃分析中，我们确定并复制了9p21.3（CDKN2B-AS1）作为儿童星形胶质细胞瘤的风险位点，从而建立了第一个基因组范围内常见变异易感性在儿童神经肿瘤学中的显著证据。此外，我们通过展示与降低脑组织CDKN2B表达的可能联系提出了一个功能基础，并证实遗传易感性在低级别和高级别星形胶质细胞瘤之间存在差异。© 作者（2023）。由牛津大学出版社代表神经肿瘤学协会出版。

While recent sequencing studies have revealed that 10% of childhood gliomas are caused by rare germline mutations, the role of common variants is undetermined and no genome-wide significant risk loci for pediatric CNS tumors have been identified to date.Meta-analysis of three population-based genome-wide association studies (GWASs) comprising 4,069 children with glioma and 8,778 controls of multiple genetic ancestries. Replication was performed in a separate case-control cohort. Quantitative trait loci analyses and a transcriptome-wide association study were conducted to assess possible links with brain tissue expression across 18,628 genes.Common variants in CDKN2B-AS1 at 9p21.3 were significantly associated with astrocytoma, the most common subtype of glioma in children (rs573687, p-value 6.974e-10, OR 1.273, CI95 1.179-1.374). The association was driven by low-grade astrocytoma (p-value 3.815e-9) and exhibited unidirectional effects across all six genetic ancestries. For glioma overall, the association approached genome-wide significance (rs3731239, p-value 5.411e-8), while no significant association was observed for high-grade tumors. Predicted decreased brain tissue expression of CDKN2B was significantly associated with astrocytoma (p-value 8.090e-8).In this population-based GWAS meta-analysis, we identify and replicate 9p21.3 (CDKN2B-AS1) as a risk locus for childhood astrocytoma, thereby establishing the first genome-wide significant evidence of common variant predisposition in pediatric neuro-oncology. We furthermore provide a functional basis for the association by showing a possible link to decreased brain tissue CDKN2B expression and substantiate that genetic susceptibility differs between low- and high-grade astrocytoma.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.