Multi-ancestry single-cell eQTL map of lupus identifies regulatory variants missed by bulk analyses

Researchers have posted a preprint to bioRxiv presenting SLEmap, a multi-ancestry single-cell expression quantitative trait locus (sc-eQTL) map built from peripheral blood mononuclear cells derived from 281 patients with systemic lupus erythematosus (SLE). The dataset yields 18,608 independent eQTLs across 5,656 genes.

Of particular note, 149 signals in 66 genes colocalise with established SLE genome-wide association study (GWAS) loci. Critically, the authors report that nearly half of these colocalised signals were detectable only through cell-type-level analyses — that is, they would have been invisible in conventional bulk-tissue eQTL studies. This underscores the value of single-cell resolution for translating GWAS hits into specific regulatory mechanisms and candidate genes.

The multi-ancestry design is a deliberate methodological choice aimed at improving the generalisability of findings beyond predominantly European-ancestry cohorts, which have historically dominated eQTL catalogues. The preprint describes which ancestries are represented, though the available lede does not enumerate them.

SLEmap adds to a growing ecosystem of disease-specific single-cell regulatory maps — analogous to efforts in inflammatory bowel disease and rheumatoid arthritis — that pair genomic and transcriptomic data to prioritise candidates for functional follow-up. As a preprint, the findings await peer review.