Improved allele frequencies in gnomAD through local ancestry inference.
Authors | |
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. |
Year of Publication | 2025
|
Journal | Nature communications
|
Volume | 16
|
Issue | 1
|
Pages | 8734
|
Date Published | 10/2025
|
ISSN | 2041-1723
|
DOI | 10.1038/s41467-025-63340-2
|
PubMed ID | 41053080
|
Links |