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

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 Amer...

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Published inPLoS genetics Vol. 18; no. 9; p. e1010388
Main Authors Li, Shaobo, Chiang, Charleston W K, Myint, Swe Swe, Arroyo, Katti, Chan, Tsz Fung, Morimoto, Libby, Metayer, Catherine, de Smith, Adam J, Walsh, Kyle M, Wiemels, Joseph L
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 07.09.2022
Public Library of Science (PLoS)
Subjects
Admixture mapping
Analysis
Astrocytoma
Astrocytoma - genetics
Biology and Life Sciences
Brain cancer
Brain tumors
Child
Children
Chromosome Mapping
Chromosomes
Cultural differences
Gene mapping
Genetic aspects
Genome-Wide Association Study
Genomes
Genomics
Hispanic American children
Hispanic Americans
Hispanic or Latino - genetics
Humans
Identification and classification
Mann-Whitney U test
Medicine and Health Sciences
Methods
Mutation
Pediatrics
People and Places
Physical Sciences
Polymorphism, Single Nucleotide - genetics
Research and Analysis Methods
Single-nucleotide polymorphism
United States
United States > US
California
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Abstract 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.
AbstractList BackgroundPilocytic 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.MethodsWe 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.ResultsWe 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.ConclusionsThere is a significant difference in genomic ancestry associated with Latino PA risk and several genomic loci potentially mediating this risk.
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.sup.-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.
Background 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. Methods 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. Results 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.sup.-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. Conclusions There is a significant difference in genomic ancestry associated with Latino PA risk and several genomic loci potentially mediating this risk.
Background 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. Methods 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. Results 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. Conclusions There is a significant difference in genomic ancestry associated with Latino PA risk and several genomic loci potentially mediating this risk.
Background 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. Methods 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. Results 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. Conclusions There is a significant difference in genomic ancestry associated with Latino PA risk and several genomic loci potentially mediating this risk.
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.
Childhood brain tumors are among the most prevalent and lethal childhood cancers. Despite this, the epidemiology as well as genetic risks are not well defined. For example, children of European ancestry have a higher risk of contracting pilocytic astrocytoma (PA) compared to other ancestries, but the genetic or environmental basis for this is unknown. Latino children are a mixture of multiple ancestries including European, African, and Native American. Using a group of Californian Latino children, we show that the risk of PA increases when a Latino child has a higher proportion of European ancestry. This global ancestry difference shows that germline genetic risk alleles contribute to a higher PA risk in children of European descendent. Moreover, this ancestral risk is localized to specific regions of the genome, especially in Chromosome 6 near the SNX14 gene, which is associated with cancer-related growth signaling pathway described by MAPK/ERK. This result brings us one step closer to understanding the etiology of this common childhood brain tumor.
Background 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. Methods 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. Results 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. Conclusions There is a significant difference in genomic ancestry associated with Latino PA risk and several genomic loci potentially mediating this risk.
Audience Academic
Author Walsh, Kyle M
Myint, Swe Swe
Li, Shaobo
Metayer, Catherine
Wiemels, Joseph L
Chan, Tsz Fung
de Smith, Adam J
Morimoto, Libby
Arroyo, Katti
Chiang, Charleston W K
AuthorAffiliation University Hospital of the Canton Vaud (CHUV), SWITZERLAND
1 Center for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, United States of America
3 School of Public Health, University of California Berkeley, Berkeley, California, United States of America
4 Division of Neuro-Epidemiology, Department of Neurosurgery, Duke University, Durham, North Carolina, United States of America
2 Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, California, United States of America
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CitedBy_id crossref_primary_10_1016_j_xhgg_2023_100239
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Snippet 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...
Background Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. PA has at least a 50% higher incidence in populations of European ancestry...
Background Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. PA has at least a 50% higher incidence in populations of European ancestry...
BACKGROUNDPilocytic astrocytoma (PA) is the most common pediatric brain tumor. PA has at least a 50% higher incidence in populations of European ancestry...
Childhood brain tumors are among the most prevalent and lethal childhood cancers. Despite this, the epidemiology as well as genetic risks are not well defined....
BackgroundPilocytic astrocytoma (PA) is the most common pediatric brain tumor. PA has at least a 50% higher incidence in populations of European ancestry...
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SourceType Open Website
Open Access Repository
Aggregation Database
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StartPage e1010388
SubjectTerms Admixture mapping
Analysis
Astrocytoma
Astrocytoma - genetics
Biology and Life Sciences
Brain cancer
Brain tumors
Child
Children
Chromosome Mapping
Chromosomes
Cultural differences
Gene mapping
Genetic aspects
Genome-Wide Association Study
Genomes
Genomics
Hispanic American children
Hispanic Americans
Hispanic or Latino - genetics
Humans
Identification and classification
Mann-Whitney U test
Medicine and Health Sciences
Methods
Mutation
Pediatrics
People and Places
Physical Sciences
Polymorphism, Single Nucleotide - genetics
Research and Analysis Methods
Single-nucleotide polymorphism
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Title Localized variation in ancestral admixture identifies pilocytic astrocytoma risk loci among Latino children
URI https://www.ncbi.nlm.nih.gov/pubmed/36070312
https://www.proquest.com/docview/2725275644/abstract/
https://search.proquest.com/docview/2711306636
https://pubmed.ncbi.nlm.nih.gov/PMC9484652
https://doaj.org/article/fd422ec2c6d84881bc7daf32d74b12c0
http://dx.doi.org/10.1371/journal.pgen.1010388
Volume 18
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