{"doi":"10.1093/neuonc/noad042","title":"Multi-ancestry genome-wide association study of 4069 children with glioma identifies 9p21.3 risk locus","abstract":"BACKGROUND: Although 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 central nervous system tumors have been identified to date. METHODS: Meta-analysis of 3 population-based genome-wide association studies comprising 4069 children with glioma and 8778 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. RESULTS: Common variants in CDKN2B-AS1 at 9p21.3 were significantly associated with astrocytoma, the most common subtype of glioma in children (rs573687, P-value of 6.974e-10, OR 1.273, 95% CI 1.179-1.374). The association was driven by low-grade astrocytoma (P-value of 3.815e-9) and exhibited unidirectional effects across all 6 genetic ancestries. For glioma overall, the association approached genome-wide significance (rs3731239, P-value of 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 of 8.090e-8). CONCLUSIONS: In this population-based genome-wide association study 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.","journal":"Neuro-Oncology","year":2023,"id":342309,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7133,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":653515,"name":"Shaobo Li","orcid":"0000-0002-0544-5338","position":1,"is_corresponding":false},{"id":1078816,"name":"Adam Rosenbaum","orcid":"0009-0003-2316-477X","position":2,"is_corresponding":false},{"id":1078817,"name":"Christian M. Hagen","orcid":"0000-0002-0513-7722","position":3,"is_corresponding":false},{"id":1078818,"name":"Ulrik Kristoffer Stoltze","orcid":"0000-0001-5862-3292","position":4,"is_corresponding":false},{"id":1079295,"name":"Sally Ljungqvist","orcid":null,"position":5,"is_corresponding":false},{"id":440341,"name":"Ulf Hjalmars","orcid":"0000-0002-9281-8744","position":6,"is_corresponding":false},{"id":361906,"name":"Kjeld Schmiegelow","orcid":"0000-0002-0829-4993","position":7,"is_corresponding":false},{"id":480846,"name":"Libby M. Morimoto","orcid":"0000-0002-1509-739X","position":8,"is_corresponding":false},{"id":107666,"name":"Adam J. de Smith","orcid":"0000-0003-4880-7543","position":9,"is_corresponding":false},{"id":1078819,"name":"René Mathiasen","orcid":"0000-0003-3782-7776","position":10,"is_corresponding":false},{"id":480847,"name":"Catherine Metayer","orcid":"0000-0003-3467-4145","position":11,"is_corresponding":false},{"id":5235,"name":"David M. Hougaard","orcid":"0000-0001-5928-3517","position":12,"is_corresponding":false},{"id":264803,"name":"Beatrice Melin","orcid":"0000-0002-9982-3757","position":13,"is_corresponding":false},{"id":338823,"name":"Kyle M. Walsh","orcid":"0000-0002-5879-9981","position":14,"is_corresponding":false},{"id":5372,"name":"Jonas Bybjerg‐Grauholm","orcid":"0000-0003-1705-4008","position":15,"is_corresponding":false},{"id":440330,"name":"Anna M. Dahlin","orcid":"0000-0002-6754-2571","position":16,"is_corresponding":false},{"id":409685,"name":"Joseph L. Wiemels","orcid":"0000-0003-4838-9951","position":17,"is_corresponding":false},{"id":1078815,"name":"Jon Foss-Skiftesvik","orcid":"0000-0002-0259-8128","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:11:12.506815Z","pmid":"36810956","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}