Language
English
Publication Date
10-6-2025
Journal
Nature Communications
DOI
10.1038/s41467-025-63340-2
PMID
41053080
PMCID
PMC12500861
PubMedCentral® Posted Date
10-6-2025
PubMedCentral® Full Text Version
Post-print
Abstract
The Genome Aggregation Database (gnomAD) is a foundational resource for allele frequency data, widely used in genomic research and clinical interpretation. However, traditional estimates rely on individual-level genetic ancestry groupings that may obscure variation in recently admixed populations. To improve resolution, we applied local ancestry inference (LAI) to over 27 million variants in two admixed groups: Admixed American (n = 7612) and African/African American (n = 20,250), deriving ancestry-specific allele frequencies. We show that 78.5% and 85.1% of variants in these groups, respectively, exhibit at least a twofold difference in ancestry-specific frequencies. Moreover, 81.49% of variants with LAI information would be assigned a higher gnomAD-wide maximum frequency after incorporating LAI, potentially altering clinical interpretations. This LAI-informed release reveals clinically relevant frequency differences that are masked in aggregate estimates and may support reclassifying some variants from Uncertain Significance to Benign or Likely Benign.
Keywords
Humans, Black or African American, Databases, Genetic, Gene Frequency, Genetics, Population, Genome, Human, Genomics, Polymorphism, Single Nucleotide, European People, American Indian or Alaska Native, Haplotypes, Genetic databases, Genetic variation
Published Open-Access
yes
Recommended Citation
Kore, Pragati; Wilson, Michael W; Tiao, Grace; et al., "Improved Allele Frequencies in Gnomad Through Local Ancestry Inference" (2025). Faculty and Staff Publications. 5017.
https://digitalcommons.library.tmc.edu/baylor_docs/5017
Included in
Genetic Phenomena Commons, Genetic Processes Commons, Genetic Structures Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons