European genetic ancestry associated with risk of childhood ependymoma.

Journal Article (Journal Article)

BACKGROUND: Ependymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk in US populations. METHODS: In a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among recently admixed Hispanic and African American subjects and estimated European admixture among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local ancestry. We also evaluated race/ethnicity-stratified ependymoma incidence data from the Central Brain Tumor Registry of the United States (CBTRUS). RESULTS: CBTRUS data revealed that African American and Native American children have 33% and 36%, respectively, reduced incidence of ependymoma compared with non-Hispanic whites. In genetic analyses, a 20% increase in European ancestry was associated with a 1.31-fold higher odds of ependymoma among self-reported Hispanics and African Americans (95% CI: 1.08-1.59, Pmeta = 6.7 × 10-3). Additionally, eastern European ancestral substructure was associated with increased ependymoma risk in non-Hispanic whites (P = 0.030) and in Hispanics (P = 0.043). Admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and targeted fine-mapping identified a lead variant at rs6039499 near RSPO4 (odds ratio = 1.99; 95% CI: 1.45-2.73; P = 2.2 × 10-5) but which was not validated in an independent set of posterior fossa type A patients. CONCLUSIONS: Interethnic differences in ependymoma risk are recapitulated in the genomic ancestry of ependymoma patients, implicating regions to target in future association studies.

Full Text

Duke Authors

Cited Authors

  • Zhang, C; Ostrom, QT; Hansen, HM; Gonzalez-Maya, J; Hu, D; Ziv, E; Morimoto, L; de Smith, AJ; Muskens, IS; Kline, CN; Vaksman, Z; Hakonarson, H; Diskin, SJ; Kruchko, C; Barnholtz-Sloan, JS; Ramaswamy, V; Ali-Osman, F; Bondy, ML; Taylor, MD; Metayer, C; Wiemels, JL; Walsh, KM

Published Date

  • November 26, 2020

Published In

Volume / Issue

  • 22 / 11

Start / End Page

  • 1637 - 1646

PubMed ID

  • 32607579

Pubmed Central ID

  • PMC7846152

Electronic International Standard Serial Number (EISSN)

  • 1523-5866

Digital Object Identifier (DOI)

  • 10.1093/neuonc/noaa130

Language

  • eng

Conference Location

  • England