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 worlds 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 databases 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.