Single-cell multi-ancestry regulatory map of systemic lupus erythematosus
- 1Sanger Institute, Wellcome Genome Campus, Hinxton, UK; Open Targets, Wellcome Genome Campus, Hinxton, UK
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-{kappa}B 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.
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BibTeX
@misc{jang2026singlecell,
title = {{Single-cell multi-ancestry regulatory map of systemic lupus erythematosus}},
author = {H. Jang and C. Sutherland and W. Lee and N. de Klein and T. S. Rupall and B. L. Chau and E. V. Buyamin and N. Buang and M. West and C. Wincup and K. L. Burnham and E. R. Holzinger and S. Middleton and F. Nestle and E. de Rinaldis and M. C. Pickering and M. Botto and C. P. Jones and T. J. Vyse and J. E. Peters and G. Trynka and E. E. Davenport},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.18.752560},
url = {https://www.biorxiv.org/content/10.64898/2026.09.18.752560v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Single-cell multi-ancestry regulatory map of systemic lupus erythematosus
AU - H. Jang
AU - C. Sutherland
AU - W. Lee
AU - N. de Klein
AU - T. S. Rupall
AU - B. L. Chau
AU - E. V. Buyamin
AU - N. Buang
AU - M. West
AU - C. Wincup
AU - K. L. Burnham
AU - E. R. Holzinger
AU - S. Middleton
AU - F. Nestle
AU - E. de Rinaldis
AU - M. C. Pickering
AU - M. Botto
AU - C. P. Jones
AU - T. J. Vyse
AU - J. E. Peters
AU - G. Trynka
AU - E. E. Davenport
PY - 2026
DA - 2026/09/18
PB - bioRxiv
DO - 10.64898/2026.09.18.752560
UR - https://www.biorxiv.org/content/10.64898/2026.09.18.752560v1
AB - 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-{kappa}B 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.
ER -