Evidence map›Paper›PMID 36810956›Full record

SynthesisNeuro-oncology2023

Multi-ancestry genome-wide association study of 4069 children with glioma identifies 9p21.3 risk locus.

Jon Foss-Skiftesvik, Shaobo Li, Adam Rosenbaum, Christian Munch Hagen, Ulrik Kristoffer Stoltze, Sally Ljungqvist, Ulf Hjalmars, Kjeld Schmiegelow, Libby Morimoto, Adam J de Smith and 8 more

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.2field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
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  6. Article
  7. Article
  8. Maternal Prenatal Use of Alcohol, Tobacco, and Illicit Drugs and Associations with Childhood Cancer Subtypes.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024
    Article
  9. Risk locus for paediatric astrocytoma identified.Nature reviews. Neurology · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 3 countries.

Jon Foss-SkiftesvikDepartment of Neurosurgery, Rigshospitalet University Hospital, Copenhagen, Denmark.ORCID 0000-0002-0259-8128
Shaobo LiCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, USA.ORCID 0000-0002-0544-5338
Adam RosenbaumDepartment of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Christian Munch HagenSection for Neonatal Genetics, Statens Serum Institute, Copenhagen, Denmark.
Ulrik Kristoffer StoltzeDepartment of Pediatrics and Adolescent Medicine, Rigshospitalet University Hospital, Copenhagen, Denmark.
Sally LjungqvistDepartment of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Ulf HjalmarsDepartment of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Kjeld SchmiegelowDepartment of Pediatrics and Adolescent Medicine, Rigshospitalet University Hospital, Copenhagen, Denmark.ORCID 0000-0002-0829-4993
Libby MorimotoCenter for Personalized Medicine, Children's Hospital of Los Angeles, Los Angeles, California, USA.ORCID 0000-0002-1509-739X
Adam J de SmithCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, USA.
René MathiasenDepartment of Pediatrics and Adolescent Medicine, Rigshospitalet University Hospital, Copenhagen, Denmark.
Catherine MetayerSchool of Public Health, University of California, Berkeley, Berkeley, California, USA.
David HougaardSection for Neonatal Genetics, Statens Serum Institute, Copenhagen, Denmark.
Beatrice MelinDepartment of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Kyle M WalshDivision of Neuro-Epidemiology, Department of Neurosurgery, Duke University, Durham, North Carolina, USA.
Jonas Bybjerg-GrauholmSection for Neonatal Genetics, Statens Serum Institute, Copenhagen, Denmark.
Anna M DahlinDepartment of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Joseph L WiemelsCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, USA.
Umeå University · SEStatens Serum Institut · DKRigshospitalet · DKUniversity of Southern California · USBerkeley Public Health Division · USChildren's Hospital of Los Angeles · USDuke University · US

Funding

CALIFORNIA COORDINATED CANCER PREVENTION & CONTROL PROGRAMU58DP003862 · DP · CALIFORNIA STATE DEPT OF PUBLIC HEALTH · PI SNIPES, KURT P · 2012 to 2014
$31.5M
Targeted Alpha-Particle Radiotheraphy of Brain Tumors with 211At-81C6 AntibodyP50CA190991 · NCI · DUKE UNIVERSITY · PI ALI-OSMAN, FRANCIS, ASHLEY, DAVID M. · 2014 to 2023
$20.8M
International Case Control Study of Malignant GliomaR01CA139020 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BONDY, MELISSA L. · 2010 to 2015
$16.0M
Genetic Susceptibility to Pediatric Glioma inIndividuals and Diverse populationsR01CA194189 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI WALSH, KYLE M, WIEMELS, JOSEPH LEO · 2015 to 2020
$5.0M
NCCDPHP CDC HHS U58 DP003862NCI NIH HHS HHSN261201000034CNCI NIH HHS HHSN261201000035CNCI NIH HHS HHSN261201000140CNCI NIH HHS P50 CA190991NCI NIH HHS R01 CA139020NCI NIH HHS R01 CA194189
6 · The paper itself

Abstract

backgroundAlthough 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.

methodsMeta-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.

resultsCommon 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).

conclusionsIn 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.

Indexed as

AstrocytomaGliomaRNA, Long NoncodingChildGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansPolymorphism, Single NucleotideRNA, Long NoncodingChildhood brain tumorsgenetic susceptibilitygliomaGWASpediatric neuro-oncology

Identifiers

PMID36810956
PMCPMC10484172
OpenAlexW4321469469

What OpenQuestion holds

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LicenceCC BY-NC
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.