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Platelet function is modified by common sequence variation in megakaryocyte super enhancers.
Petersen, Romina; Lambourne, John J; Javierre, Biola M; Grassi, Luigi; Kreuzhuber, Roman; Ruklisa, Dace; Rosa, Isabel M; Tomé, Ana R; Elding, Heather; van Geffen, Johanna P; Jiang, Tao; Farrow, Samantha; Cairns, Jonathan; Al-Subaie, Abeer M; Ashford, Sofie; Attwood, Antony; Batista, Joana; Bouman, Heleen; Burden, Frances; Choudry, Fizzah A; Clarke, Laura; Flicek, Paul; Garner, Stephen F; Haimel, Matthias; Kempster, Carly; Ladopoulos, Vasileios; Lenaerts, An-Sofie; Materek, Paulina M; McKinney, Harriet; Meacham, Stuart; Mead, Daniel; Nagy, Magdolna; Penkett, Christopher J; Rendon, Augusto; Seyres, Denis; Sun, Benjamin; Tuna, Salih; van der Weide, Marie-Elise; Wingett, Steven W; Martens, Joost H; Stegle, Oliver; Richardson, Sylvia; Vallier, Ludovic; Roberts, David J; Freson, Kathleen; Wernisch, Lorenz; Stunnenberg, Hendrik G; Danesh, John; Fraser, Peter; Soranzo, Nicole.
Affiliation
  • Petersen R; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Lambourne JJ; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Javierre BM; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Grassi L; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Kreuzhuber R; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • Ruklisa D; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Rosa IM; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Tomé AR; NIHR BioResource-Rare Diseases, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Elding H; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • van Geffen JP; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Jiang T; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Farrow S; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Cairns J; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Al-Subaie AM; Medical Research Council Biostatistics Unit, University of Cambridge, Forvie Site, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK.
  • Ashford S; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Attwood A; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Batista J; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Bouman H; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Burden F; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Choudry FA; Strangeways 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.
  • Clarke L; Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
  • Flicek P; Strangeways Research Laboratory, MRC/British Heart Foundation (BHF) Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • Garner SF; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Haimel M; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Kempster C; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • Ladopoulos V; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Lenaerts AS; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Materek PM; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Dammam, P.O. Box 1982, Dammam 31441, Saudi Arabia.
  • McKinney H; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Meacham S; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Mead D; NIHR BioResource-Rare Diseases, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Nagy M; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Penkett CJ; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Rendon A; NIHR BioResource-Rare Diseases, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Seyres D; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Sun B; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Tuna S; Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • van der Weide ME; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Wingett SW; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Martens JH; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Stegle O; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Richardson S; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Vallier L; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Roberts DJ; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Freson K; NIHR BioResource-Rare Diseases, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Wernisch L; Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Stunnenberg HG; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Danesh J; National Health Service Blood and Transplant (NHSBT), Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Fraser P; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Soranzo N; NIHR Cambridge Biomedical Research Centre hIPSC Core Facility, Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0SZ, UK.
Nat Commun ; 8: 16058, 2017 07 13.
Article in En | MEDLINE | ID: mdl-28703137
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genetic Variation / Blood Platelets / Megakaryocytes / Erythroblasts / Enhancer Elements, Genetic Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2017 Document type: Article Affiliation country: Reino Unido
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genetic Variation / Blood Platelets / Megakaryocytes / Erythroblasts / Enhancer Elements, Genetic Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2017 Document type: Article Affiliation country: Reino Unido