New gene functions in megakaryopoiesis and platelet formation. (Articolo in rivista)

Type
Label
  • New gene functions in megakaryopoiesis and platelet formation. (Articolo in rivista) (literal)
Anno
  • 2011-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1038/nature10659 (literal)
Alternative label
  • Christian Gieger1*, Aparna Radhakrishnan2,3*, Ana Cvejic2,3*, Weihong Tang4*, Eleonora Porcu5*, Giorgio Pistis6*, Jovana Serbanovic-Canic2,3*, Ulrich Elling7, Alison H. Goodall8,9, Yann Labrune10, Lorna M. Lopez11,12, Reedik Ma¨gi13,28, Stuart Meacham2,3, Yukinori Okada14,15, Nicola Pirastu16,102, Rossella Sorice17, Alexander Teumer18, Katrin Voss2, Weihua Zhang19, Ramiro Ramirez-Solis3, Joshua C. Bis20, David Ellinghaus21, Martin Go¨ gele22, Jouke-Jan Hottenga23, Claudia Langenberg24, Peter Kovacs25, Paul F. O'Reilly26, So-Youn Shin3,27, To~nu Esko28,29,30, Jaana Hartiala31,32, Stavroula Kanoni3,33, Federico Murgia34, Afshin Parsa35, Jonathan Stephens2, Pim van der Harst36, C. Ellen van der Schoot37, Hooman Allayee31,32, Antony Attwood2,3, Beverley Balkau38,39, François Bastardot40, Saonli Basu41, Sebastian E. Baumeister42, Ginevra Biino34,43,44, Lorenzo Bomba45, Ame´lie Bonnefond10, François Cambien46, John C. Chambers19, Francesco Cucca5, Pio D'Adamo16,102, Gail Davies12, Rudolf A. de Boer36, Eco J. C. de Geus23, Angela Do¨ ring47,48, Paul Elliott19,49, Jeanette Erdmann50,101, David M. Evans51, Mario Falchi52, Wei Feng41, Aaron R. Folsom4, Ian H. Frazer53, Quince D. Gibson35, Nicole L. Glazer54, Chris Hammond27, Anna-Liisa Hartikainen55, Susan R. Heckbert56,57, Christian Hengstenberg58, Micha Hersch59, Thomas Illig60, Ruth J. F. Loos24, Jennifer Jolley2, Kay Tee Khaw61,62, Brigitte Ku¨hnel1, Marie-Christine Kyrtsonis63, Vasiliki Lagou64, Heather Lloyd-Jones2, Thomas Lumley65, Massimo Mangino27, Andrea Maschio5, Irene Mateo Leach36, Barbara McKnight65, Yasin Memari3,27, Braxton D. Mitchell35, Grant W. Montgomery66, Yusuke Nakamura67, Matthias Nauck68, Gerjan Navis69, Ute No¨ thlings70,71, Ilja M. Nolte72, David J. Porteous11,73, Anneli Pouta55,74, Peter P. Pramstaller22, Janne Pullat28, Susan M. Ring51, Jerome I. Rotter75, Daniela Ruggiero17, Aimo Ruokonen76, Cinzia Sala6, Nilesh J. Samani8,9, Jennifer Sambrook2,77, David Schlessinger78, Stefan Schreiber21, Heribert Schunkert50,101, James Scott79, Nicholas L. Smith56,57,80, Harold Snieder72, John M. Starr11,81, Michael Stumvoll82, Atsushi Takahashi14, W. H. Wilson Tang83,84, Kent Taylor75, Albert Tenesa85,86, Swee Lay Thein87, Anke To¨njes82, Manuela Uda5, Sheila Ulivi16, Dirk J. van Veldhuisen36, Peter M. Visscher11,66, Uwe Vo¨lker18, H.-Erich Wichmann47,88, Kerri L. Wiggins20, Gonneke Willemsen23, Tsun-Po Yang3, Jing Hua Zhao24, Paavo Zitting89, John R. Bradley77, George V. Dedoussis33, Paolo Gasparini16,102, Stanley L. Hazen83, Andres Metspalu28,29,30, Mario Pirastu34,43, Alan R. Shuldiner35,90, L. Joost van Pelt91, Jaap-Jan Zwaginga92, Dorret I.Boomsma23, Ian J. Deary11,12, Andre Franke21, Philippe Froguel10,52, Santhi K. Ganesh93, Marjo-Riitta Jarvelin26,94,95, Nicholas G. Martin66, Christa Meisinger48, Bruce M. Psaty57,96, Timothy D. Spector27, Nicholas J. Wareham24, Jan-Willem N. Akkerman97, Marina Ciullo17, Panos Deloukas3, Andreas Greinacher98, Steve Jupe99, Naoyuki Kamatani14, Jyoti Khadake99, Jaspal S. Kooner79, Josef Penninger7, Inga Prokopenko64, Derek Stemple3, Daniela Toniolo6,44, Lorenz Wernisch100, Serena Sanna5*, Andrew A. Hicks22*, Augusto Rendon2,100*, Manuel A. Ferreira 66*, Willem H. Ouwehand 2,3,77* & Nicole Soranzo3* (2011)
    New gene functions in megakaryopoiesis and platelet formation.
    in Nature (Lond.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Christian Gieger1*, Aparna Radhakrishnan2,3*, Ana Cvejic2,3*, Weihong Tang4*, Eleonora Porcu5*, Giorgio Pistis6*, Jovana Serbanovic-Canic2,3*, Ulrich Elling7, Alison H. Goodall8,9, Yann Labrune10, Lorna M. Lopez11,12, Reedik Ma¨gi13,28, Stuart Meacham2,3, Yukinori Okada14,15, Nicola Pirastu16,102, Rossella Sorice17, Alexander Teumer18, Katrin Voss2, Weihua Zhang19, Ramiro Ramirez-Solis3, Joshua C. Bis20, David Ellinghaus21, Martin Go¨ gele22, Jouke-Jan Hottenga23, Claudia Langenberg24, Peter Kovacs25, Paul F. O'Reilly26, So-Youn Shin3,27, To~nu Esko28,29,30, Jaana Hartiala31,32, Stavroula Kanoni3,33, Federico Murgia34, Afshin Parsa35, Jonathan Stephens2, Pim van der Harst36, C. Ellen van der Schoot37, Hooman Allayee31,32, Antony Attwood2,3, Beverley Balkau38,39, François Bastardot40, Saonli Basu41, Sebastian E. Baumeister42, Ginevra Biino34,43,44, Lorenzo Bomba45, Ame´lie Bonnefond10, François Cambien46, John C. Chambers19, Francesco Cucca5, Pio D'Adamo16,102, Gail Davies12, Rudolf A. de Boer36, Eco J. C. de Geus23, Angela Do¨ ring47,48, Paul Elliott19,49, Jeanette Erdmann50,101, David M. Evans51, Mario Falchi52, Wei Feng41, Aaron R. Folsom4, Ian H. Frazer53, Quince D. Gibson35, Nicole L. Glazer54, Chris Hammond27, Anna-Liisa Hartikainen55, Susan R. Heckbert56,57, Christian Hengstenberg58, Micha Hersch59, Thomas Illig60, Ruth J. F. Loos24, Jennifer Jolley2, Kay Tee Khaw61,62, Brigitte Ku¨hnel1, Marie-Christine Kyrtsonis63, Vasiliki Lagou64, Heather Lloyd-Jones2, Thomas Lumley65, Massimo Mangino27, Andrea Maschio5, Irene Mateo Leach36, Barbara McKnight65, Yasin Memari3,27, Braxton D. Mitchell35, Grant W. Montgomery66, Yusuke Nakamura67, Matthias Nauck68, Gerjan Navis69, Ute No¨ thlings70,71, Ilja M. Nolte72, David J. Porteous11,73, Anneli Pouta55,74, Peter P. Pramstaller22, Janne Pullat28, Susan M. Ring51, Jerome I. Rotter75, Daniela Ruggiero17, Aimo Ruokonen76, Cinzia Sala6, Nilesh J. Samani8,9, Jennifer Sambrook2,77, David Schlessinger78, Stefan Schreiber21, Heribert Schunkert50,101, James Scott79, Nicholas L. Smith56,57,80, Harold Snieder72, John M. Starr11,81, Michael Stumvoll82, Atsushi Takahashi14, W. H. Wilson Tang83,84, Kent Taylor75, Albert Tenesa85,86, Swee Lay Thein87, Anke To¨njes82, Manuela Uda5, Sheila Ulivi16, Dirk J. van Veldhuisen36, Peter M. Visscher11,66, Uwe Vo¨lker18, H.-Erich Wichmann47,88, Kerri L. Wiggins20, Gonneke Willemsen23, Tsun-Po Yang3, Jing Hua Zhao24, Paavo Zitting89, John R. Bradley77, George V. Dedoussis33, Paolo Gasparini16,102, Stanley L. Hazen83, Andres Metspalu28,29,30, Mario Pirastu34,43, Alan R. Shuldiner35,90, L. Joost van Pelt91, Jaap-Jan Zwaginga92, Dorret I.Boomsma23, Ian J. Deary11,12, Andre Franke21, Philippe Froguel10,52, Santhi K. Ganesh93, Marjo-Riitta Jarvelin26,94,95, Nicholas G. Martin66, Christa Meisinger48, Bruce M. Psaty57,96, Timothy D. Spector27, Nicholas J. Wareham24, Jan-Willem N. Akkerman97, Marina Ciullo17, Panos Deloukas3, Andreas Greinacher98, Steve Jupe99, Naoyuki Kamatani14, Jyoti Khadake99, Jaspal S. Kooner79, Josef Penninger7, Inga Prokopenko64, Derek Stemple3, Daniela Toniolo6,44, Lorenz Wernisch100, Serena Sanna5*, Andrew A. Hicks22*, Augusto Rendon2,100*, Manuel A. Ferreira 66*, Willem H. Ouwehand 2,3,77* & Nicole Soranzo3* (literal)
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  • PMID: 22139419 doi:10.1038/nature10659 (literal)
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  • 1Institute of Genetic Epidemiology, Helmholtz Zentrum Mu¨nchen, German Research Center for Environmental Health, Ingolsta¨dter Landstr.1, 85764 Neuherberg, Germany. 2Department of Haematology, University of Cambridge & NHS Blood and Transplant, Cambridge CB2 0PT, UK. 3Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH/1SA,UK. 4Division ofEpidemiology and Community Health,University of Minnesota, Minneapolis, Minnesota 55455-0354, USA. 5Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari 09042, Italy. 6San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy. 7IMBA, Institute ofMolecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria. 8Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK. 9Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK. 10CNRS-UMR-8199, Institut de Biologie de Lille, 1 Rue du Professor Calmette, BP245, 59019 Lille Cedex, France. 11Centre for Cognitive Ageing and Cognitive Epidemiology, 7 George Square, The University of Edinburgh, Edinburgh EH8 9JZ, UK. 12Department of Psychology, The University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK. 13Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. 14Laboratory for Statistical Analysis, RIKEN Center for Genomic Medicine, Institute ofPhysical andChemical Research, 1-7-22Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. 15Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8654, Japan. 16Institute for Maternal and Child Health--IRCCS 'Burlo Garofolo'--via dell'Istria 65/1, 34137 Trieste, Italy. 17Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, Via P. Castellino 111, 8031 Naples, Italy. 18Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, 17487 Greifswald, Germany. 19Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, St Mary's Campus, London W2 1PG, UK. 20Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, Washington 98195-0001, USA. 21Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24105 Kiel, Germany. 22Centre for Biomedicine, EuropeanAcademyBozen/Bolzano, Viale Druso 1,39100Bolzano, Italy. 23Department of Biological Psychology, VU University Amsterdam, De Boelelaan 1105, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands. 24MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Box 285, Cambridge CB2 0QQ, UK. 25Interdisciplinary Centre for Clinical Research, University of Leipzig, Inselstr. 22, 04103 Leipzig, Germany. 26Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK. 27Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. 28Estonian Genome Center, University of Tartu, Tiigi 61b, 50410 Tartu, Estonia. 29Estonian Biocenter, Riia 23b, 51010, Tartu, Estonia. 30Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. 31Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089-9075, USA. 32Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089-9075, USA. 33Department of Nutrition-Dietetics, Harokopio University, Athens 17671, Greece. 34Institute of Population Genetics, National Council of Research, 07100 Sassari, Italy. 35University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, Maryland 21201-1559, USA. 36Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. 37Department of Experimental Immunohaematology, Sanquin Research, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands and Landsteiner Laboratory, AcademicMedical Centre,University ofAmsterdam,Meibergdreef 9,1105AZ Amsterdam, The Netherlands. 38Inserm, CESP Centre for research in Epidemiology and PopulationHealth,U1018Villejuif,94807France. 39University ParisSud11,UMRS1018, Villejuif, 94807 France. 40Service de Me´decine Interne, CHUV, 1011 Lausanne, Switzerland. 41Division of Biostatistics, School of Public Health, University of Minnesota, A460 Mayo Building, mmc 303, 420 Delaware St SE, Minneapolis, Minnesota 55455, USA. 42Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, 17475 Greifswald, Germany. 43Shardna Life Sciences, Loc. Piscinamanna 09010 Pula (CA), Italy. 44Institute of Molecular Genetics-CNR Via Abbiategrasso 207, 27100 Pavia, Italy. 45Istituto di Zootecnica, Universita' Cattolica del Sacro Cuore sede Piacenza, via Emilia Parmense 84,29122Piacenza, Italy. 46INSERMUMRS 937, Pierre and Marie Curie University (UPMC, Paris 6) and Medical School, 91 Bd de l'Ho^pital, 75013 Paris, France. 47Institute of Epidemiology I, Helmholtz Zentrum Mu¨nchen, German Research Center for Environmental Health, Ingolsta¨dter Landstr.1, 85764 Neuherberg, Germany. 48Institute of Epidemiology II, Helmholtz Zentrum Mu¨nchen, German Research Center for Environmental Health, Ingolsta¨dter Landstr.1, 85764Neuherberg, Germany. 49MRC-HPA Centre for Environment and Health, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK. 50Universita¨t zu Lu¨beck, Medizinische Klinik 2, Lu¨beck Germany. 51MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. 52Department of Genomics of Common Disease, School of Public Health, Imperial College London, The Commonwealth Building, The Hammersmith Hospital, Du Care Road, London W12 ONN, UK. 53The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia. 54Department of Medicine, Boston University, Boston, Massachusetts 02118, USA. 55Department of Clinical Sciences/Obstetrics and Gynecology, University of Oulu, Aapistie 7, Oulu, 90220 Finland. 56Department of Epidemiology, University of Washington, Seattle, Washington 98195-7236, USA. 57Group Health Research Institute, Group Health Cooperative, Seattle,Washington 98101-1448, USA. 58Klinik und Poliklinik fu¨ r Innere Medizin II, Universita¨tsklinikum Regensburg, 93053 Regensburg, Germany. 59Department of Medical Genetics, University of Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland. 60Unit for Molecular Epidemiology, Helmholtz Zentrum Mu¨nchen, German Research Center for Environmental Health, Ingolsta¨dter Landstr.1, 85764 Neuherberg, Germany. 61Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge CB1 8RN, UK. 62Clinical Gerontology Unit, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. 63First Department of Propedeutic Internal Medicine and Hematology Department, National and Kapodistrian University of Athens Medical School, Laikon GeneralHospital, Athens11727, Greece. 64OxfordCentre for Diabetes,Endocrinologyand Metabolism, University of Oxford, Oxford OX3 7LJ, UK. 65Department of Biostatistics, University of Washington, Seattle, Washington 98195-7232, USA. 66Genetic Epidemiology, Queensland Institute of Medical Research, The Bancroft Centre, 300 Herston Road, Herston 4006,Queensland, Australia. 67Laboratory ofMolecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. 68Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt-University Greifswald, 17475 Greifswald, Germany. 69Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands. 70Section for Epidemiology, Institute for Experimental Medicine, Christian-Albrechts-University Kiel, 24105 Kiel, Germany. 71Popgen Biobank, University Clinic Schleswig-Holstein, 24105 Kiel, Germany. 72Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands. 73Medical Genetics Section, University of Edinburgh,MolecularMedicine Centre,Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK. 74National Institute for Health and Welfare, Aapistie 1, Oulu 90220, Finland. 75Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 76Institute of Diagnostics, Clinical Chemistry, University of Oulu, Box 5000Y, University of Oulu, Oulu 90014, Finland. 77NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK. 78Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland 21224-6825, USA. 79Faculty of Medicine, National Heart and Lung Institute, Cardiovascular Science, Hammersmith Campus, Hammersmith Hospital, Imperial College London, London W12 0HS, UK. 80Seattle Epidemiologic Research and Information Center of the Department of Veterans Affairs Office of Research and Development, Seattle, Washington 98108, USA. 81Geriatric Medicine Unit, The University of Edinburgh, Royal Victoria, Craigleith Road, Edinburgh EH4 2DN, UK. 82Department of Medicine, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany. 83Center for Cardiovascular Diagnostics and Prevention, Department of Cell Biology and Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA. 84Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. 85Institute of Genetics and Molecular Medicine, MRC Human Genetics Unit, Edinburgh EH4 2XU, UK. 86The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin Midlothian EH25 9RG, UK. 87Department of Molecular Haematology, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK. 88Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universita¨t and KlinikumGrosshadern, Marchioninistr. 15, 81377 Munich, Germany. 89Department of Physiatrics, Lapland Central Hospital, Rovaniemi, 96101, Finland. 90Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland 21208, USA. 91Department of Laboratory Medicine, UniversityMedical Center Groningen, University of Groningen, 9713 GZ, Groningen, TheNetherlands. 92Sanquin Research Leiden, Jon J. van Rood Center for Clinical Transfusion research, and the Department of Immuno-hematology and Blood Transfusion, Leiden University Medical Center, 2333 Leiden, The Netherlands. 93Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, Michigan, USA. 94Institute of Health Sciences, University of Oulu, Aapistie 7, Oulu, 90220 Finland. 95National Institute for Health and Welfare, Biocenter Oulu, University of Oulu, Aapistie 7, Oulu, 90220 Finland. 96Department of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington 98101-1448, USA. 97Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands. 98Institute for Immunology andTransfusionMedicine, Ernst-Moritz-Arndt-University Greifswald,17475 Greifswald, Germany. 99Proteomics Services, EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. 100MRC Biostatistics Unit, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge CB2 0SR, UK. 101Nordic Center of Cardiovascular Research, Lubeck, Germany. 102University of Trieste, Piazzale Europa 1, 34127 Trieste, Italy. *These authors contributed equally to this work. (literal)
Titolo
  • New gene functions in megakaryopoiesis and platelet formation. (literal)
Abstract
  • Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. (literal)
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