ArticleFrontiers in immunology2019
Functional Annotation of Genetic Loci Associated With Sepsis Prioritizes Immune and Endothelial Cell Pathways.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 16 citations in OpenAlex.
- eQTLs identify regulatory networks and drivers of variation in the individual response to sepsis.Cell genomics · 2024Article
- A scalable Bayesian functional GWAS method accounting for multivariate quantitative functional annotations with applications for studying Alzheimer disease.HGG advances · 2022Article
- Single-cell RNA-sequencing of peripheral blood mononuclear cells reveals widespread, context-specific gene expression regulation upon pathogenic exposure.Nature communications · 2022Article
- The rs8506 TT Genotype inFrontiers in public health · 2022Article
- Body mass index, time of day and genetics affect perivascular spaces in the white matter.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Genetic Predisposition to the Mortality in Septic Shock Patients: From GWAS to the Identification of a Regulatory Variant Modulating the Activity of aInternational journal of molecular sciences · 2021Article
- Leukocyte-Released Mediators in Response to Both Bacterial and Fungal Infections Trigger IFN Pathways, Independent of IL-1 and TNF-α, in Endothelial Cells.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to limited sepsis patient cohort size and extreme heterogeneity, only one significant locus and suggestive associations at several independent loci were implicated by three genome-wide association studies. However, genes from such suggestive loci may also provide crucial information to unravel genetic mechanisms that determine sepsis heterogeneity. Therefore, in this study, we made use of integrative approaches to prioritize genes and pathways affected by sepsis associated genetic variants. By integrating expression quantitative trait loci (eQTL) results from the largest whole-blood eQTL database, cytokine QTLs from pathogen-stimulated peripheral blood mononuclear cells (PBMCs), publicly available blood transcriptome data from pneumoniae-derived sepsis patients, and transcriptome data from pathogen-stimulated PBMCs, we identified 55 potential genes affected by 39 independent loci. By performing pathway enrichment analysis at these loci we found enrichment of genes for adherences-junction pathway. Finally, we investigated the functional role of the only one GWAS significant SNP rs4957796 on sepsis survival in altering transcription factor binding affinity in monocytes and endothelial cells. We also found that transient deficiency of
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