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Genome-wide association analysis identifies a meningioma risk locus at 11p15.5

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  • Elizabeth B Claus
  • Alex J Cornish
  • Peter Broderick
  • Joellen M Schildkraut
  • Sara E Dobbins
  • Amy Holroyd
  • Lisa Calvocoressi
  • Lingeng Lu
  • Helen M Hansen
  • Ivan Smirnov
  • Kyle M Walsh
  • Johannes Schramm
  • Per Hoffmann
  • Markus M Nöthen
  • Karl-Heinz Jöckel
  • Anthony Swerdlow
  • Signe Benzon Larsen
  • Christoffer Johansen
  • Matthias Simon
  • Melissa Bondy
  • Margaret Wrensch
  • Richard Houlston
  • Joseph L Wiemels
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BACKGROUND: Meningioma 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 two GWAS, imputed using a merged reference panel of 1,000 Genomes and UK10K data, with validation in two independent sample series totaling 2,138 cases and 12,081 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.

Original languageEnglish
JournalNeuro-Oncology
Volume20
Issue number11
Pages (from-to)1485-1493
ISSN1522-8517
DOIs
Publication statusPublished - 2018
Externally publishedYes

ID: 54867062