ArticleGenome medicine2022
Integrating single-cell sequencing data with GWAS summary statistics reveals CD16+monocytes and memory CD8+T cells involved in severe COVID-19.
Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
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- Human autoimmunity at single cell resolution in aplastic anemia before and after effective immunotherapy.Nature communications · 2025Article
- MixOmics Integration of Biological Datasets Identifies Highly Correlated Variables of COVID-19 Severity.International journal of molecular sciences · 2025Article
- Integrating microbial GWAS and single-cell transcriptomics reveals associations between host cell populations and the gut microbiome.Nature microbiology · 2025Article
- Systematic dissection of pleiotropic loci and critical regulons in excitatory neurons and microglia relevant to neuropsychiatric and ocular diseases.Translational psychiatry · 2025Article
- Neutrophils restricted contribution ofHeliyon · 2025Article
- Advanced omics approaches in liver transplant settings: current applications and future prospectives.Frontiers in immunology · 2025Review
- Chemokines as potential biomarkers for predicting the course of COVID-19 - a review of the literature.Frontiers in immunology · 2025Review
- Exploring of bladder cancer immune-related genes and potential therapeutic targets based on transcriptomic data and Mendelian randomization analysis.Frontiers in immunology · 2025Article
- Exploring genetic loci linked to COVID-19 severity and immune response through multi-trait GWAS analyses.Frontiers in genetics · 2025Article
- Machine learning integrative approaches to advance computational immunology.Genome medicine · 2024Review
- Integration of human organoids single-cell transcriptomic profiles and human genetics repurposes critical cell type-specific drug targets for severe COVID-19.Cell proliferation · 2024Article
- Immune characteristics of kidney transplant recipients with acute respiratory distress syndrome induced by COVID-19 at single-cell resolution.Respiratory research · 2024Article
- Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19.Frontiers in immunology · 2024Article
- GWAS and polygenic risk score of severe COVID-19 in Eastern Europe.Frontiers in medicine · 2024Article
- Causal relationship between the gut microbiota, immune cells, and coronary heart disease: a mediated Mendelian randomization analysis.Frontiers in microbiology · 2024Article
- Single-cell transcriptomic landscape reveals the role of intermediate monocytes in aneurysmal subarachnoid hemorrhage.Frontiers in cell and developmental biology · 2024Article
- Gut microbiota influence on lung cancer risk through blood metabolite mediation: from a comprehensive Mendelian randomization analysis and genetic analysis.Frontiers in nutrition · 2024Article
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUnderstanding the host genetic architecture and viral immunity contributes to the development of effective vaccines and therapeutics for controlling the COVID-19 pandemic. Alterations of immune responses in peripheral blood mononuclear cells play a crucial role in the detrimental progression of COVID-19. However, the effects of host genetic factors on immune responses for severe COVID-19 remain largely unknown.
methodsWe constructed a computational framework to characterize the host genetics that influence immune cell subpopulations for severe COVID-19 by integrating GWAS summary statistics (N = 969,689 samples) with four independent scRNA-seq datasets containing healthy controls and patients with mild, moderate, and severe symptom (N = 606,534 cells). We collected 10 predefined gene sets including inflammatory and cytokine genes to calculate cell state score for evaluating the immunological features of individual immune cells.
resultsWe found that 34 risk genes were significantly associated with severe COVID-19, and the number of highly expressed genes increased with the severity of COVID-19. Three cell subtypes that are CD16+monocytes, megakaryocytes, and memory CD8+T cells were significantly enriched by COVID-19-related genetic association signals. Notably, three causal risk genes of CCR1, CXCR6, and ABO were highly expressed in these three cell types, respectively. CCR1
conclusionsWe uncover a major genetics-modulated immunological shift between mild and severe infection, including an elevated expression of genetics-risk genes, increase in inflammatory cytokines, and of functional immune cell subsets aggravating disease severity, which provides novel insights into parsing the host genetic determinants that influence peripheral immune cells in severe COVID-19.
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