A Global Atlas of Immune Alleles Reveals Health-Relevant Variation Across Groups
- 1Variant Bio Inc.
Abstract
Immune allele frequencies inform disease association mapping, pharmacogenomic guidance, and vaccine design, yet such data are missing for most of the world's groups. Here we present the Global Atlas of Immune Alleles (GAIA), applying benchmarked genotyping tools across the Human Leukocyte Antigen (HLA), Immunoglobulin Heavy Chain Constant (IGHC), and Fc Gamma Receptor (FCGR) loci to whole-genome sequencing data from 20,248 individuals, oversampling sub-Saharan African, Island Southeast Asian, and Pacific groups. Despite representing fewer than 0.5% of observations in the Allele Frequency Net Database, GAIA expands the database's catalogue by 38%, demonstrating that representation matters more than sample size. We identify HLA alleles at group-specific frequencies that challenge pharmacogenomic screening recommendations and document disease-risk alleles common in groups lacking clinical guidance. Finally, we introduce majority allelic diversity (MAD-X), which counts the alleles required for X% of individuals in a group to carry at least one, and show that reaching 90% HLA-B coverage for vaccine design requires up to 2.7 times more alleles in underrepresented groups than in those of Northwest European ancestry.
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BibTeX
@misc{harvey2026global,
title = {{A Global Atlas of Immune Alleles Reveals Health-Relevant Variation Across Groups}},
author = {W. T. Harvey and A.-K. Emde and F. E. Kakembo and I. Hamid and W. E. Clarke and I. Apriyana and H. Babiker and R. Rakotoarivony and M. Hendershott and P. Kasina and A. Kalungi and O. Ojewunmi and T. Pascart and S. Rosso and R. A. Verdugo and C. Ferreccio and A. Dessein and P. Kusuma and L. Priliani and S. G. Malik and J. Fabian and M. Ramsay and K. A. Wasik and K. Fox and T. R. Merriman and S. Fatumo and H. Sudoyo and L. Yerges-Armstrong and S. E. Castel},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.02.26367118},
url = {https://www.medrxiv.org/content/10.64898/2026.11.02.26367118v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - A Global Atlas of Immune Alleles Reveals Health-Relevant Variation Across Groups
AU - W. T. Harvey
AU - A.-K. Emde
AU - F. E. Kakembo
AU - I. Hamid
AU - W. E. Clarke
AU - I. Apriyana
AU - H. Babiker
AU - R. Rakotoarivony
AU - M. Hendershott
AU - P. Kasina
AU - A. Kalungi
AU - O. Ojewunmi
AU - T. Pascart
AU - S. Rosso
AU - R. A. Verdugo
AU - C. Ferreccio
AU - A. Dessein
AU - P. Kusuma
AU - L. Priliani
AU - S. G. Malik
AU - J. Fabian
AU - M. Ramsay
AU - K. A. Wasik
AU - K. Fox
AU - T. R. Merriman
AU - S. Fatumo
AU - H. Sudoyo
AU - L. Yerges-Armstrong
AU - S. E. Castel
PY - 2026
DA - 2026/11/02
PB - medRxiv
DO - 10.64898/2026.11.02.26367118
UR - https://www.medrxiv.org/content/10.64898/2026.11.02.26367118v1
AB - Immune allele frequencies inform disease association mapping, pharmacogenomic guidance, and vaccine design, yet such data are missing for most of the world's groups. Here we present the Global Atlas of Immune Alleles (GAIA), applying benchmarked genotyping tools across the Human Leukocyte Antigen (HLA), Immunoglobulin Heavy Chain Constant (IGHC), and Fc Gamma Receptor (FCGR) loci to whole-genome sequencing data from 20,248 individuals, oversampling sub-Saharan African, Island Southeast Asian, and Pacific groups. Despite representing fewer than 0.5% of observations in the Allele Frequency Net Database, GAIA expands the database's catalogue by 38%, demonstrating that representation matters more than sample size. We identify HLA alleles at group-specific frequencies that challenge pharmacogenomic screening recommendations and document disease-risk alleles common in groups lacking clinical guidance. Finally, we introduce majority allelic diversity (MAD-X), which counts the alleles required for X% of individuals in a group to carry at least one, and show that reaching 90% HLA-B coverage for vaccine design requires up to 2.7 times more alleles in underrepresented groups than in those of Northwest European ancestry.
ER -