Genetics

Three recent MS genetics papers, compared by the job each gives to single-cell or single-nucleus RNA sequencing, since the direction of travel between a variant and a cell decides what a study can claim. Giordano and colleagues found a HIF1A locus in 2,817 patients tied to a more favourable course past 20 years, then used single-nucleus and spatial data to show the variant acting in a cell-type-specific, context-dependent way. King and colleagues went the other way: longitudinal single-cell sequencing gave a monocyte and B cell signature up to three months before relapse, enriched for EBV lytic response genes, and only afterwards did MS GWAS risk loci and EBNA-2-bound enhancers enter as an annotation. Yan and colleagues measured nothing, joining public expression data to eQTLGen cis-eQTLs and IMSGC statistics to retain ARHGAP25, HLA-DRB1, MERTK, MS4A6A and SYK while dropping SAMSN1 and XBP1 for pointing against the expression evidence. The close sets out what each design settles and the step all three leave open.