Publication Date
1-15-2026
Journal
Human Genetics and Genomics Advances
DOI
10.1016/j.xhgg.2025.100534
PMID
41261530
PMCID
PMC12664375
PubMedCentral® Posted Date
10-25-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with Hispanic/Latino children having a higher incidence of ALL than other racial/ethnic groups. Among the genetic variants previously implicated in ALL risk, a number of them were found to be enriched in Indigenous American (IA)-like ancestries and inherited by many Hispanic/Latino individuals. However, due to potential confounding from environmental factors, the association between IA-like ancestry and risk for ALL has remained unclear. In this study, we characterized the impact of IA-like ancestry on overall ALL risk and on the frequency and effect size of known risk alleles, while accounting for non-genetic correlates of ancestry. Contrary to previous findings, we found that global IA-like ancestry was not significantly associated with ALL risk after adjusting for socioeconomic indicators. However, locally at known ALL risk regions, we uncovered that increasing copies of the IA-like haplotype were positively and significantly associated with ALL risk (e.g., the IA-like haplotype had ∼1.33 times the odds of harboring the risk allele compared to non-IA-like haplotypes), but we found no evidence of interaction between genotype and ancestry in relation to ALL. Admixture mapping identified replicable association signals at chr7p12.2 and chr10q21.2, consistent with the benefit of leveraging genetic ancestry in identifying genetic risk loci. Our results suggest that increased risk of ALL in Hispanic/Latino children may be conferred by the higher frequency of risk alleles within IA-like ancestry and that local ancestry-based analyses are robust strategies to elucidate genetic etiology of disease.
Keywords
Humans, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Hispanic or Latino, Child, Male, Female, Genetic Predisposition to Disease, Haplotypes, Child, Preschool, Alleles, Risk Factors, Polymorphism, Single Nucleotide, Adolescent, White, acute lymphoblastic leukemia, cancer, admixture, admixture mapping, ancestry, complex trait, socio-economic status
Published Open-Access
yes
Recommended Citation
Langie, Jalen; Chan, Tsz Fung; Yang, Wenjian; et al., "The Impact of Indigenous American-Like Ancestry on the Risk of Acute Lymphoblastic Leukemia in Hispanic/Latino Children" (2026). Faculty, Staff and Students Publications. 6375.
https://digitalcommons.library.tmc.edu/baylor_docs/6375