eQTLs identify regulatory networks and drivers of variation in the individual response to sepsis.
Cell Genom
; 4(7): 100587, 2024 Jul 10.
Article
en En
| MEDLINE
| ID: mdl-38897207
ABSTRACT
Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection, for which disease heterogeneity is a major obstacle to developing targeted treatments. We have previously identified gene-expression-based patient subgroups (sepsis response signatures [SRS]) informative for outcome and underlying pathophysiology. Here, we aimed to investigate the role of genetic variation in determining the host transcriptomic response and to delineate regulatory networks underlying SRS. Using genotyping and RNA-sequencing data on 638 adult sepsis patients, we report 16,049 independent expression (eQTLs) and 32 co-expression module (modQTLs) quantitative trait loci in this disease context. We identified significant interactions between SRS and genotype for 1,578 SNP-gene pairs and combined transcription factor (TF) binding site information (SNP2TFBS) and predicted regulon activity (DoRothEA) to identify candidate upstream regulators. Overall, these approaches identified putative mechanistic links between host genetic variation, cell subtypes, and the individual transcriptomic response to infection.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Sepsis
/
Polimorfismo de Nucleótido Simple
/
Sitios de Carácter Cuantitativo
/
Redes Reguladoras de Genes
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Cell Genom
Año:
2024
Tipo del documento:
Article
País de afiliación:
Reino Unido