Unveiling genetic signatures of immune response in immune-related diseases through single-cell eQTL analysis across diverse conditions

Zhenhua Zhang, Wenchao Li, Qiuyao Zhan, Michelle Aillaud, Javier Botey-Bataller, Martijn Zoodsma, Rob Horst, Leo A. B. Joosten, Christoph Bock, Leon N. Schulte, Cheng-Jian Xu, Mihai G. Netea, Marc Jan Bonder and Yang Li ()
Additional contact information
Zhenhua Zhang: a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)
Wenchao Li: a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)
Qiuyao Zhan: a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)
Michelle Aillaud: Philipps University
Javier Botey-Bataller: a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)
Martijn Zoodsma: a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)
Rob Horst: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Leo A. B. Joosten: Radboud University Medical Center
Christoph Bock: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Leon N. Schulte: Philipps University
Cheng-Jian Xu: a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)
Mihai G. Netea: Radboud University Medical Center
Marc Jan Bonder: University Medical Center Groningen
Yang Li: a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Deciphering the intricate regulatory mechanisms underlying biological processes holds promise for elucidating how genetic variants contribute to immune-related disorders. We map genetic effects on gene expression (expression quantitative trait locus, eQTL) using single-cell transcriptomes of 152 samples from 38 healthy individuals, covering baseline state and lipopolysaccharide challenge either before or after Bacillus Calmette-Guerin vaccination. Interestingly, we uncover a monocyte eQTL linked to the LCP1, shedding light on inter-individual variations in trained immunity. Furthermore, we elucidate genetic and epigenetic regulatory networks of CD55 and SLFN5. Of note, our results support the pivotal roles of SLFN5 in COVID-19 pathogenesis by incorporating disease-associated loci, chromatin accessibility, and transcription factor binding affinities, aligning with the established functions of SLFN5 in restricting virus replication during viral infection. Our study provides a paradigm to decipher genetic underpinnings of complex traits by integrating single-cell eQTLs with multi-omics data from patients and public databases.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61192-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61192-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-61192-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().