ArticlePloS one2017
SNP in human ARHGEF3 promoter is associated with DNase hypersensitivity, transcript level and platelet function, and Arhgef3 KO mice have increased mean platelet volume.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Mean platelet volume levels in children with sleep-disordered breathing: a meta-analysis.BMC pediatrics · 2020Pooled it
- Integrating Polygenic Risk and Ocular Phenotyping Reveals an Axial-Length-Dominant Mechanism in High and Extreme High Myopia.Ophthalmology science · 2026Article
- Integrated transcriptome and single-cell RNA sequencing identifies small GTPase-associated biomarkers in ulcerative colitis.Frontiers in immunology · 2026Article
- The Rho GTPase regulator ARHGEF3 orchestrates hair placode budding by coordinating cell fate and P-cadherin patterning in mice.PLoS biology · 2026Article
- BayesCNet: Bayesian inference for cell type-specific regulatory networks leveraging cell type hierarchy in single-cell data.bioRxiv : the preprint server for biology · 2025Article
- ARHGEF3 Regulates Hair Follicle Morphogenesis.bioRxiv : the preprint server for biology · 2024Article
- Trans-eQTL mapping in gene sets identifies network effects of genetic variants.Cell genomics · 2024Article
- Article
- Genomic Variation Affecting MPV and PLT Count in Association with Development of Ischemic Stroke and Its Subtypes.Molecular neurobiology · 2023Article
- Interplay between hereditary and acquired factors determines the neutrophil counts in older individuals.Blood advances · 2023Article
- Analysis of genetic dominance in the UK Biobank.Science (New York, N.Y.) · 2023Article
- Uncovering potential diagnostic biomarkers of acute myocardial infarction based on machine learning and analyzing its relationship with immune cells.BMC cardiovascular disorders · 2023Article
- Secondary analyses for genome-wide association studies using expression quantitative trait loci.Genetic epidemiology · 2022Article
- Role of ARHGEF3 as a GEF and mTORC2 Regulator.Frontiers in cell and developmental biology · 2021Review
- Analysis of Population Structure and Differentially Selected Regions in Guangxi Native Breeds by Restriction Site Associated with DNA Sequencing.G3 (Bethesda, Md.) · 2020Article
- Arhgef1 Plays a Vital Role in Platelet Function and Thrombogenesis.Journal of the American Heart Association · 2019Article
- Article
- SelectedClinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
Genome-wide association studies have identified a genetic variant at 3p14.3 (SNP rs1354034) that strongly associates with platelet number and mean platelet volume in humans. While originally proposed to be intronic, analysis of mRNA expression in primary human hematopoietic subpopulations reveals that this SNP is located directly upstream of the predominantly expressed ARHGEF3 isoform in megakaryocytes (MK). We found that ARHGEF3, which encodes a Rho guanine exchange factor, is dramatically upregulated during both human and murine MK maturation. We show that the SNP (rs1354034) is located in a DNase I hypersensitive region in human MKs and is an expression quantitative locus (eQTL) associated with ARHGEF3 expression level in human platelets, suggesting that it may be the causal SNP that accounts for the variations observed in human platelet traits and ARHGEF3 expression. In vitro human platelet activation assays revealed that rs1354034 is highly correlated with human platelet activation by ADP. In order to test whether ARHGEF3 plays a role in MK development and/or platelet function, we developed an Arhgef3 KO/LacZ reporter mouse model. Reflecting changes in gene expression, LacZ expression increases during MK maturation in these mice. Although Arhgef3 KO mice have significantly larger platelets, loss of Arhgef3 does not affect baseline MK or platelets nor does it affect platelet function or platelet recovery in response to antibody-mediated platelet depletion compared to littermate controls. In summary, our data suggest that modulation of ARHGEF3 gene expression in humans with a promoter-localized SNP plays a role in human MKs and human platelet function-a finding resulting from the biological follow-up of human genetic studies. Arhgef3 KO mice partially recapitulate the human phenotype.
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Registered trials
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.