Genetics

This post covers three papers that read MS genetic risk through single-cell data rather than bulk tissue. Fujimoto and colleagues report a Japanese GWAS of 688 cases against 205,199 controls with MHC associations and a population-specific variant at 11q24, a cross-population meta-analysis of 29,374 cases and 1,843,563 controls over four ancestries yielding 22 novel loci, risk enrichment in the CD4 T helper lineage, regulatory T cells and endothelial cells, and spatial transcriptomics showing spatial and temporal heterogeneity of risk associations inside subcortical lesions. King and colleagues follow blood longitudinally in relapsing-remitting MS and find a reproducible monocyte and B cell signature up to three months before clinical onset, enriched for host genes responsive to EBV lytic reactivation factors, with raised LMP-1 transcripts in pre-relapse B cells and expansion of CD11c-positive atypical B cells displaying gp350; the pre-relapse modules overlap MS GWAS loci and EBNA-2-bound enhancers, while the authors state that the link to CNS lesion formation remains to be established. Jones and colleagues sequence 480 lymphoblastoid cell lines, find about 1,200 sex-biased genes with only 7.7 per cent explained by sex-chromosome number and 79 per cent as targets of sex-biased transcription factors, and map 2,390 sex-biased eQTLs enriched across more than 100 GWAS phenotypes including MS, with modest independent confirmation.