TY  - JOUR
AU  - Zhang, Zhenhua
AU  - Li, Wenchao
AU  - Zhan, Qiuyao
AU  - Aillaud, Michelle
AU  - Botey-Bataller, Javier
AU  - Zoodsma, Martijn
AU  - Ter Horst, Rob
AU  - Joosten, Leo A B
AU  - Bock, Christoph
AU  - Schulte, Leon N
AU  - Xu, Cheng-Jian
AU  - Netea, Mihai G
AU  - Bonder, Marc Jan
AU  - Li, Yang
TI  - Unveiling genetic signatures of immune response in immune-related diseases through single-cell eQTL analysis across diverse conditions.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-01626
SP  - 7134
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Quantitative Trait Loci: genetics
KW  - Single-Cell Analysis: methods
KW  - COVID-19: immunology
KW  - COVID-19: genetics
KW  - COVID-19: virology
KW  - SARS-CoV-2: immunology
KW  - Transcriptome
KW  - Male
KW  - Female
KW  - Gene Regulatory Networks
KW  - Monocytes: immunology
KW  - Monocytes: metabolism
KW  - Immune System Diseases: genetics
KW  - Immune System Diseases: immunology
KW  - Adult
KW  - Immunity: genetics
KW  - Genetic Predisposition to Disease
LB  - PUB:(DE-HGF)16
C6  - pmid:40759647
DO  - DOI:10.1038/s41467-025-61192-4
UR  - https://inrepo02.dkfz.de/record/303377
ER  -