Unveiling genetic signatures of immune response in immune-related diseases through single-cell eQTL analysis across diverse conditions
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.
Authors
- Leon N. Schulte (ORCID: https://orcid.org/0000-0001-6814-9344)
- Marc Jan Bonder (ORCID: https://orcid.org/0000-0002-8431-3180)
- Martijn Zoodsma (ORCID: https://orcid.org/0000-0003-3636-2209)
- Rob ter Horst (ORCID: https://orcid.org/0000-0003-0576-5873)
- Mihai Gheorghe Netea (ORCID: https://orcid.org/0000-0003-2421-6052)
- Leo A. B. Joosten (ORCID: https://orcid.org/0000-0001-6166-9830)
- Michelle Aillaud
- Zhenhua Zhang (ORCID: https://orcid.org/0000-0002-1781-7127)
- Cheng‐Jian Xu (ORCID: https://orcid.org/0000-0003-1586-4672)
- Christoph Bock (ORCID: https://orcid.org/0000-0001-6091-3088)
- Qiuyao Zhan
- Javier Botey-Bataller (ORCID: https://orcid.org/0000-0003-3512-3150)
- Wenchao Li (ORCID: https://orcid.org/0000-0002-7956-0742)
- Yang Li (ORCID: https://orcid.org/0000-0003-4022-7341)
Institutions
- University Medical Center Groningen (NL)
- University of Bonn (DE)
- Austrian Academy of Sciences (AT)
- Radboud University Nijmegen (NL)
- Philipps University of Marburg (DE)
- Austrian Research Institute for Artificial Intelligence (AT)
- University of Groningen (NL)
- German Cancer Research Center (DE)
- Iuliu Hațieganu University of Medicine and Pharmacy (RO)
- Heidelberg University (DE)
- Radboud University Medical Center (NL)
- Medizinische Hochschule Hannover (DE)
- Radboud Institute for Molecular Life Sciences (NL)
- Oncode Institute (NL)
- Helmholtz Centre for Infection Research (DE)
- CeMM Research Center for Molecular Medicine (AT)
- German Center for Lung Research (DE)
- European Molecular Biology Laboratory (DE)
- Centre for Individualised Infection Medicine (DE)
- Center for Experimental and Clinical Infection Research (DE)
- Artificial Intelligence in Medicine (Canada) (CA)
- Medical University of Vienna (AT)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-04
- DOI
- https://doi.org/10.1038/s41467-025-61192-4
- Citations
- 2
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- European Commission
- Deutsche Forschungsgemeinschaft
- Radboud Universiteit
- China Scholarship Council
- Radboud Universitair Medisch Centrum
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Human Genome Research Institute
- NIH Office of the Director
- National Cancer Institute
- National Institute of Neurological Disorders and Stroke
- Common Fund