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| Home > Publications database > Unveiling genetic signatures of immune response in immune-related diseases through single-cell eQTL analysis across diverse conditions. |
| Journal Article | DKFZ-2025-01626 |
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2025
Springer Nature
[London]
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Please use a persistent id in citations: 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.
Keyword(s): Humans (MeSH) ; Quantitative Trait Loci: genetics (MeSH) ; Single-Cell Analysis: methods (MeSH) ; COVID-19: immunology (MeSH) ; COVID-19: genetics (MeSH) ; COVID-19: virology (MeSH) ; SARS-CoV-2: immunology (MeSH) ; Transcriptome (MeSH) ; Male (MeSH) ; Female (MeSH) ; Gene Regulatory Networks (MeSH) ; Monocytes: immunology (MeSH) ; Monocytes: metabolism (MeSH) ; Immune System Diseases: genetics (MeSH) ; Immune System Diseases: immunology (MeSH) ; Adult (MeSH) ; Immunity: genetics (MeSH) ; Genetic Predisposition to Disease (MeSH)
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