A Global Atlas of Immune Alleles Reveals Health-Relevant Variation Across Groups
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.
Authors
- Isabella Apriyana (ORCID: https://orcid.org/0000-0002-5195-7254)
- Tristan Pascart (ORCID: https://orcid.org/0000-0002-8395-826X)
- Herawati Sudoyo (ORCID: https://orcid.org/0000-0002-7567-4929)
- June Fabian (ORCID: https://orcid.org/0000-0001-7130-9142)
- William T. Harvey (ORCID: https://orcid.org/0000-0001-9529-1127)
- Michele Lee Ramsay (ORCID: https://orcid.org/0000-0002-4156-4801)
- Tony Raymond Merriman (ORCID: https://orcid.org/0000-0003-0844-8726)
- Laura M. Yerges-Armstrong (ORCID: https://orcid.org/0000-0003-0006-5237)
- Melissa C. Hendershott (ORCID: https://orcid.org/0000-0002-4769-2548)
- Iman Hamid (ORCID: https://orcid.org/0000-0003-2168-9727)
- Fredrick Elishama Kakembo (ORCID: https://orcid.org/0000-0002-7962-5454)
- Anne‐Katrin Emde (ORCID: https://orcid.org/0000-0003-2553-2225)
- Prathap Kasina
- Ricardo A. Verdugo (ORCID: https://orcid.org/0000-0001-5668-5449)
- Stephane E. Castel (ORCID: https://orcid.org/0000-0002-0707-2133)
- Pradiptajati Kusuma (ORCID: https://orcid.org/0000-0002-9722-4048)
- Kaja A. Wasik (ORCID: https://orcid.org/0009-0002-2789-0974)
- Safarina G. Malik (ORCID: https://orcid.org/0000-0002-7258-2586)
- Allan Kalungi (ORCID: https://orcid.org/0000-0002-2890-0145)
- Keolu Fox (ORCID: https://orcid.org/0000-0003-4215-5273)
- Alain J.J. Dessein (ORCID: https://orcid.org/0000-0001-5339-2456)
- Wayne E. Clarke (ORCID: https://orcid.org/0000-0003-2471-0712)
- Lidwina Priliani (ORCID: https://orcid.org/0000-0001-6304-9571)
- Catterina Ferreccio R (ORCID: https://orcid.org/0000-0001-6331-5534)
- Segun Fatumo (ORCID: https://orcid.org/0000-0003-4525-3362)
- Rindra Rakotoarivony (ORCID: https://orcid.org/0009-0007-7006-7808)
- Hiba Babiker
- Oyesola Ojewunmi
- Stefania Rosso
Institutions
- University of Antananarivo (MG)
- Inserm (FR)
- Pontificia Universidad Católica de Chile (CL)
- Université Catholique de Lille (FR)
- University of the Witwatersrand (ZA)
- University of California San Diego (US)
- Mochtar Riady Institute for Nanotechnology (ID)
- MRC/UVRI & LSHTM Uganda Research Unit (UG)
- University of Chile (CL)
- Makerere University (UG)
- University of Otago (NZ)
- Uganda Virus Research Institute (UG)
Publication Details
- Journal
- medRxiv
- Published
- 2026-11-04
- DOI
- https://doi.org/10.64898/2026.11.02.26367118
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- preprint