Genome-wide association analysis identifies a meningioma risk locus at 11p15.5.
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Date
2018-10-09Author
Claus, EB
Cornish, AJ
Broderick, P
Schildkraut, JM
Dobbins, SE
Holroyd, A
Calvocoressi, L
Lu, L
Hansen, HM
Smirnov, I
Walsh, KM
Schramm, J
Hoffmann, P
Nöthen, MM
Jöckel, K-H
Swerdlow, A
Larsen, SB
Johansen, C
Simon, M
Bondy, M
Wrensch, M
Houlston, RS
Wiemels, JL
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: Meningiomas are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31. METHODS: To identify a susceptibility locus for meningioma, we conducted a meta-analysis of 2 GWAS, imputed using a merged reference panel from the 1000 Genomes Project and UK10K data, with validation in 2 independent sample series totaling 2138 cases and 12081 controls. RESULTS: We identified a new susceptibility locus for meningioma at 11p15.5 (rs2686876, odds ratio = 1.44, P = 9.86 × 10-9). A number of genes localize to the region of linkage disequilibrium encompassing rs2686876, including RIC8A, which plays a central role in the development of neural crest-derived structures, such as the meninges. CONCLUSIONS: This finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma.
Collections
Subject
Chromosomes, Human, Pair 11
Humans
Meningioma
Meningeal Neoplasms
Genetic Predisposition to Disease
Prognosis
Risk Factors
Case-Control Studies
Follow-Up Studies
Genotype
Linkage Disequilibrium
Polymorphism, Single Nucleotide
Adult
Aged
Middle Aged
Female
Male
Genome-Wide Association Study
Young Adult
Genetic Loci
Biomarkers, Tumor
Research team
Aetiological Epidemiology
Cancer Genomics
Language
eng
Date accepted
2018-05-08
License start date
2018-10
Citation
Neuro-oncology, 2018, 20 (11), pp. 1485 - 1493
Publisher
OXFORD UNIV PRESS INC