2. Academic Validation
  3. Unveiling genetic signatures of immune response in immune-related diseases through single-cell eQTL analysis across diverse conditions

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

  • Nat Commun. 2025 Aug 4;16(1):7134. doi: 10.1038/s41467-025-61192-4.
Zhenhua Zhang 1 2,  Wenchao Li 1 2,  Qiuyao Zhan 1 2,  Michelle Aillaud 3,  Javier Botey-Bataller 1 2 4,  Martijn Zoodsma 1 2,  Rob Ter Horst 5,  Leo A B Joosten 4 6,  Christoph Bock 5 7,  Leon N Schulte 3 8,  Cheng-Jian Xu 1 2 4 9,  Mihai G Netea 4 10,  Marc Jan Bonder 11 12 13 14,  Yang Li 15 16 17 18 19
Affiliations

Affiliations

  • 1 Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • 2 TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • 3 Institute for Lung Research, Philipps University, Marburg, Germany.
  • 4 Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
  • 5 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
  • 6 Department of Medical Genetics, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  • 7 Institute of Artificial Intelligence, Center for Medical Data Science, Medical University of Vienna, Vienna, Austria.
  • 8 German Center for Lung Research (DZL), Giessen, Germany.
  • 9 Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
  • 10 Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
  • 11 Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • 12 Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
  • 13 European Molecular Biology Laboratory, Genome Biology Unit, 69117, Heidelberg, Germany.
  • 14 Oncode Institute, Utrecht, The Netherlands.
  • 15 Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany. Yang.Li@helmholtz-hzi.de.
  • 16 TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany. Yang.Li@helmholtz-hzi.de.
  • 17 Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands. Yang.Li@helmholtz-hzi.de.
  • 18 Cluster of Excellence Resolving Infection Susceptibility (RESIST; EXC 2155), Hannover Medical School, Hannover, Germany. Yang.Li@helmholtz-hzi.de.
  • 19 Lower Saxony center for artificial intelligence and causal methods in medicine (CAIMed), Hannover, Germany. Yang.Li@helmholtz-hzi.de.
PMID: 40759647 DOI: 10.1038/s41467-025-61192-4
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.

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