%0 Journal Article
%A Zhang, Zhenhua
%A Li, Wenchao
%A Zhan, Qiuyao
%A Aillaud, Michelle
%A Botey-Bataller, Javier
%A Zoodsma, Martijn
%A Ter Horst, Rob
%A Joosten, Leo A B
%A Bock, Christoph
%A Schulte, Leon N
%A Xu, Cheng-Jian
%A Netea, Mihai G
%A Bonder, Marc Jan
%A Li, Yang
%T Unveiling genetic signatures of immune response in immune-related diseases through single-cell eQTL analysis across diverse conditions.
%J Nature Communications
%V 16
%N 1
%@ 2041-1723
%C [London]
%I Springer Nature
%M DKFZ-2025-01626
%P 7134
%D 2025
%X 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.
%K Humans
%K Quantitative Trait Loci: genetics
%K Single-Cell Analysis: methods
%K COVID-19: immunology
%K COVID-19: genetics
%K COVID-19: virology
%K SARS-CoV-2: immunology
%K Transcriptome
%K Male
%K Female
%K Gene Regulatory Networks
%K Monocytes: immunology
%K Monocytes: metabolism
%K Immune System Diseases: genetics
%K Immune System Diseases: immunology
%K Adult
%K Immunity: genetics
%K Genetic Predisposition to Disease
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40759647
%R 10.1038/s41467-025-61192-4
%U https://inrepo02.dkfz.de/record/303377