ArticleThe Journal of infectious diseases2019
A Genome-Wide Functional Genomics Approach Identifies Susceptibility Pathways to Fungal Bloodstream Infection in Humans.
Article in The Journal of infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- MUC16-dependent Renal Vascular Adhesion of Candida Promotes Tissue Invasion and Predicts Clinical Outcome in Candidemia.Research square · 2026Article
- Omics and Multiomics-Based Diagnostics for Invasive Candidiasis: Toward Precision Medicine.Molecular & cellular proteomics : MCP · 2025Review
- Plasma Proteomic Signature as a Predictor of Age Advancement in People Living With HIV.Aging cell · 2025Article
- The immune response of upper and lower airway epithelial cells to Aspergillus fumigatus and Candida albicans-derived β-glucan in Th17 type cytokine environment.Archives of microbiology · 2025Article
- Article
- Single-cell RNA-sequencing of peripheral blood mononuclear cells reveals widespread, context-specific gene expression regulation upon pathogenic exposure.Nature communications · 2022Article
- Host, pathogenic fungi and the microbiome: A genetic triangle in infection.Frontiers in immunology · 2022Article
- In vitro infection models to study fungal-host interactions.FEMS microbiology reviews · 2021Review
- Challenges and Opportunities in Understanding Genetics of Fungal Diseases: Towards a Functional Genomics Approach.Infection and immunity · 2021Review
- Impact of rare and common genetic variation in the interleukin-1 pathway on human cytokine responses.Genome medicine · 2021Article
- The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives.FEMS microbiology reviews · 2021Review
- BCG-induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next-generation vaccines.Immunological reviews · 2021Review
- Review
- Genetic Susceptibility to Fungal Infections and Links to Human Ancestry.Frontiers in genetics · 2021Review
- Comparative host transcriptome in response to pathogenic fungi identifies common and species-specific transcriptional antifungal host response pathways.Computational and structural biotechnology journal · 2021Article
- Inflammatory Protein Profiles in Plasma of Candidaemia Patients and the Contribution of Host Genetics to Their Variability.Frontiers in immunology · 2021Article
- Integrating GWAS with bulk and single-cell RNA-sequencing reveals a role for LY86 in the anti-Candida host response.PLoS pathogens · 2020Article
- Monocytes and the Host Response to Fungal Pathogens.Frontiers in cellular and infection microbiology · 2020Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundCandidemia, one of the most common causes of fungal bloodstream infection, leads to mortality rates up to 40% in affected patients. Understanding genetic mechanisms for differential susceptibility to candidemia may aid in designing host-directed therapies.
methodsWe performed the first genome-wide association study on candidemia, and we integrated these data with variants that affect cytokines in different cellular systems stimulated with Candida albicans.
resultsWe observed strong association between candidemia and a variant, rs8028958, that significantly affects the expression levels of PLA2G4B in blood. We found that up to 35% of the susceptibility loci affect in vitro cytokine production in response to Candida. Furthermore, potential causal genes located within these loci are enriched for lipid and arachidonic acid metabolism. Using an independent cohort, we also showed that the numbers of risk alleles at these loci are negatively correlated with reactive oxygen species and interleukin-6 levels in response to Candida. Finally, there was a significant correlation between susceptibility and allelic scores based on 16 independent candidemia-associated single-nucleotide polymorphisms that affect monocyte-derived cytokines, but not with T cell-derived cytokines.
conclusionsOur results prioritize the disturbed lipid homeostasis and oxidative stress as potential mechanisms that affect monocyte-derived cytokines to influence susceptibility to candidemia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.