Cross-population genomics reveal spatiocellular MS risk landscape

A multiancestry GWAS meta-analysis (Japan plus EUR, AFR, AMR) totaling about 29,374 MS cases and 1,843,563 controls identifies 22 novel susceptibility loci beyond the MHC region, including a Japanese-specific ETS1-near locus, and refines HLA signals; integrating single-cell and single-nucleus RNA sequencing of PBMCs and brain lesions, plus spatial transcriptomics of subcortical MS lesions, shows MS risk enrichment in CD4+ T helper cells, regulatory T cells and endothelial cells, with spatial and temporal heterogeneity across brain regions. The work highlights the power of diverse populations and multi-omics to illuminate MS genetics.