Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Integrating genomic and single-cell transcriptomic profiles from patient cohorts can uncover regulatory effects underlying genetic associations with disease. Here we present SLEmap, a multi-ancestry single-cell expression quantitative trait locus (sc-eQTL) map generated from peripheral blood mononuclear cells from 281 patients with systemic lupus erythematosus (SLE). We identified 18,608 independent eQTLs in 5,656 genes, of which 149 signals in 66 genes colocalized with SLE GWAS loci. Nearly half of these colocalizations were detected exclusively through cell type-level analyses, highlighting the importance of cellular context for interpreting disease-associated genetic variation. Multi-ancestry data identified regulatory signals robust across diverse ancestral backgrounds and improved signal resolution. Most colocalizations were undetectable in sc-eQTLs from a healthy cohort (OneK1K), with novel SLE colocalizations highlighting disease-relevant regulatory mechanisms across distinct cell types, including the NF-κB pathway. These findings demonstrate the value of disease-specific, multi-ancestry single-cell regulatory maps for resolving the genes and cellular mechanisms underlying disease-associated genetic variation.
Authors: Haerin Jang, Catherine Sutherland, Wanseon Lee, Niek de Klein, Tarran S. Rupall, Bess L. Chau, Eliora Violain Buyamin, Norzawani Buang, Magdalena West, Chris Wincup, Katie L. Burnham, Emily R. Holzinger, Sarah Middleton, Frank Nestle, Emanuele de Rinaldis, Matthew C. Pickering, Marina Botto, Carla P. Jones, Timothy J. Vyse, James E. Peters, Gosia Trynka, Emma E. Davenport
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7213978030