Localized variation in ancestral admixture identifies pilocytic astrocytoma risk loci among Latino children

by Shaobo Li, Charleston W. K. Chiang, Swe Swe Myint, Katti Arroyo, Tsz Fung Chan, Libby Morimoto, Catherine Metayer, Adam J. de Smith, Kyle M. Walsh, Joseph L. Wiemels

Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. PA has at least a 50% higher incidence in populations of European ancestry compared to other ancestral groups, which may be due in part to genetic differences.

We first compared the global proportions of European, African, and Amerindian ancestries in 301 PA cases and 1185 controls of self-identified Latino ethnicity from the California Biobank. We then conducted admixture mapping analysis to assess PA risk with local ancestry.

We found PA cases had a significantly higher proportion of global European ancestry than controls (case median = 0.55, control median = 0.51, P value = 3.5x10^-3). Admixture mapping identified 13 SNPs in the 6q14.3 region (SNX14) contributing to risk, as well as three other peaks approaching significance on chromosomes 7, 10 and 13. Downstream fine mapping in these regions revealed several SNPs potentially contributing to childhood PA risk.

There is a significant difference in genomic ancestry associated with Latino PA risk and several genomic loci potentially mediating this risk.