ArticleNature communications2017
Platelet function is modified by common sequence variation in megakaryocyte super enhancers.
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Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37citing papers in PubMed
5.2field-weighted citation impact, top 4% of its field
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
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- Restraining of glycoprotein VI- and integrin α2β1-dependent thrombus formation by platelet PECAM1.Cellular and molecular life sciences : CMLS · 2024Article
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- High-throughput microfluidic blood testing to phenotype genetically linked platelet disorders: an aid to diagnosis.Blood advances · 2023Article
- Regulation of Glycoprotein VI-Dependent Platelet Activation and Thrombus Formation by Heparan Sulfate Proteoglycan Perlecan.International journal of molecular sciences · 2023Article
- A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology.Nature communications · 2023Article
- Review
- Low input capture Hi-C (liCHi-C) identifies promoter-enhancer interactions at high-resolution.Nature communications · 2023Article
- SEdb 2.0: a comprehensive super-enhancer database of human and mouse.Nucleic acids research · 2023Article
- Non-coding genetic variation in regulatory elements determines thrombosis and hemostasis phenotypes.Journal of thrombosis and haemostasis : JTH · 2022Review
- G protein-coupled receptor kinase 5 regulates thrombin signaling in platelets via PAR-1.Blood advances · 2022Article
- Multiparameter platelet function analysis of bleeding patients with a prolonged platelet function analyser closure time.British journal of haematology · 2022Article
- Platelet GPVI (Glycoprotein VI) and Thrombotic Complications in the Venous System.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Multiparameter phenotyping of platelet reactivity for stratification of human cohorts.Blood advances · 2021Article
- Detecting chromosomal interactions in Capture Hi-C data with CHiCAGO and companion tools.Nature protocols · 2021Article
- Genome sequencing unveils a regulatory landscape of platelet reactivity.Nature communications · 2021Article
- Assessment of a complete and classified platelet proteome from genome-wide transcripts of human platelets and megakaryocytes covering platelet functions.Scientific reports · 2021Article
- Transfer to the clinic: refining forward programming of hPSCs to megakaryocytes for platelet production in bioreactors.Blood advances · 2021Article
- Current Understanding of the Relationship between Blood Donor Variability and Blood Component Quality.International journal of molecular sciences · 2021Review
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Authors and funding
59 authors at 11 institutions in 6 countries.
Romina PetersenDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
John J LambourneDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Biola M JavierreNuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
Luigi GrassiDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.ORCID 0000-0002-6308-7540
Roman KreuzhuberDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Dace RuklisaDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Isabel M RosaDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Ana R ToméDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Heather EldingDepartment of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Johanna P van GeffenDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
Tao JiangStrangeways Research Laboratory, MRC/British Heart Foundation (BHF) Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
Samantha FarrowDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Jonathan CairnsNuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
Abeer M Al-SubaieDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Sofie AshfordDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.ORCID 0000-0002-7941-7217
Antony AttwoodDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Joana BatistaDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Heleen BoumanDepartment of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Frances BurdenDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Fizzah A ChoudryDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Laura ClarkeEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.ORCID 0000-0002-5989-6898
Paul FlicekEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.ORCID 0000-0002-3897-7955
Stephen F GarnerNational Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Matthias HaimelNIHR BioResource-Rare Diseases, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.ORCID 0000-0002-0320-0214
Carly KempsterDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Vasileios LadopoulosDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.ORCID 0000-0002-0841-7973
An-Sofie LenaertsNIHR Cambridge Biomedical Research Centre hIPSC Core Facility, Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0SZ, UK.
Paulina M MaterekNIHR Cambridge Biomedical Research Centre hIPSC Core Facility, Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0SZ, UK.
Harriet McKinneyDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Stuart MeachamDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Daniel MeadDepartment of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Magdolna NagyDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
Christopher J PenkettDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Augusto RendonDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Denis SeyresDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.ORCID 0000-0002-2066-6980
Benjamin SunStrangeways Research Laboratory, MRC/British Heart Foundation (BHF) Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
Salih TunaDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Marie-Elise van der WeideDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.ORCID 0000-0001-5542-9216
Steven W WingettNuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
Joost H MartensFaculty of Science, Department of Molecular Biology, Radboud University, 6525GA Nijmegen, The Netherlands.
Oliver StegleEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.ORCID 0000-0002-8818-7193
Sylvia RichardsonMedical Research Council Biostatistics Unit, University of Cambridge, Forvie Site, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK.
Ludovic VallierWellcome Trust and MRC Cambridge Stem Cell Institute, Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0SZ, UK.
David J RobertsRadcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX9 3DU, UK.
Kathleen FresonDepartment of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven 3000, Belgium.
Lorenz WernischMedical Research Council Biostatistics Unit, University of Cambridge, Forvie Site, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK.
Hendrik G StunnenbergFaculty of Science, Department of Molecular Biology, Radboud University, 6525GA Nijmegen, The Netherlands.
John DaneshDepartment of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Peter FraserNuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.ORCID 0000-0002-0041-1227
Nicole SoranzoDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.ORCID 0000-0003-1095-3852
Adam S ButterworthStrangeways Research Laboratory, The National Institute for Health Research (NIHR) Blood and Transplant Unit in Donor Health and Genomics at the University of Cambridge, University of Cambridge, Cambridge CB1 8RN, UK.
Johan W HeemskerkDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
Ernest TurroDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Mikhail SpivakovNuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.ORCID 0000-0002-0383-3943
Willem H OuwehandDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
William J AstleDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Kate DownesDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Myrto KostadimaDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Mattia FrontiniDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.ORCID 0000-0001-8074-6299
National Health Service · GBUniversity of Cambridge · GBBabraham Institute · GBWellcome Sanger Institute · GBEuropean Bioinformatics Institute · GBMaastricht University · NLWellcome/MRC Cambridge Stem Cell Institute · GBRadboud University Nijmegen · NLChurchill Hospital · GBFlorida State University · USKU Leuven · BE
Funding
British Heart Foundation RG/08/014/24067Department of Health RP-PG-0310-1004European Research Council 268834Medical Research Council G0800270Medical Research Council MC_PC_12009Medical Research Council MC_U105260799Medical Research Council MC_UP_0801/1Medical Research Council MC_UU_00002/1Medical Research Council MC_UU_00002/10Medical Research Council MR/L003120/1Medical Research Council MR/L007150/1Wellcome Trust
Abstract
Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits using cell type-matched epigenomic data and promoter long-range interactions. We identify potential regulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we demonstrate, through ex vivo and proof of principle genome editing validation, that variants in super enhancers play an important role in controlling archetypical platelet functions.
Indexed as
Enhancer Elements, GeneticGenetic VariationBlood PlateletsChromatinErythroblastsHumansMegakaryocytesPromoter Regions, GeneticChromatin
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