New gene functions in megakaryopoiesis and platelet formation

Christian Gieger; Aparna Radhakrishnan; Ana Cvejic; Weihong Tang; Eleonora Porcu; Giorgio Pistis; Jovana Serbanovic-Canic; Ulrich Elling; Alison H. Goodall; Yann Labrune; Lorna M. Lopez; Reedik Maegi; Stuart Meacham; Yukinori Okada; Nicola Pirastu; Rossella Sorice; Alexander Teumer; Katrin Voss; Weihua Zhang; Ramiro Ramirez-Solis; Joshua C. Bis; David Ellinghaus; Martin Goegele; Jouke-Jan Hottenga; Claudia Langenberg; Peter Kovacs; Paul F. O'Reilly; So-Youn Shin; Toenu Esko; Jaana Hartiala; Stavroula Kanoni; Federico Murgia; Afshin Parsa; Jonathan Stephens; Pim van der Harst; C. Ellen van der Schoot; Hooman Allayee; Antony Attwood; Beverley Balkau; Francois Bastardot; Saonli Basu; Sebastian E. Baumeister; Ginevra Biino; Lorenzo Bomba; Amelie Bonnefond; Francois Cambien; John C. Chambers; Francesco Cucca; Pio D'Adamo; Gail Davies; Rudolf A. de Boer; Eco J. C. de Geus; Angela Doering; Paul Elliott; Jeanette Erdmann; David M. Evans; Mario Falchi; Wei Feng; Aaron R. Folsom; Ian H. Frazer; Quince D. Gibson; Nicole L. Glazer; Chris Hammond; Anna-Liisa Hartikainen; Susan R. Heckbert; Christian Hengstenberg; Micha Hersch; Thomas Illig; Ruth J. F. Loos; Jennifer Jolley; Kay Tee Khaw; Brigitte Kuehnel; Marie-Christine Kyrtsonis; Vasiliki Lagou; Heather Lloyd-Jones; Thomas Lumley; Massimo Mangino; Andrea Maschio; Irene Mateo Leach; Barbara McKnight; Yasin Memari; Braxton D. Mitchell; Grant W. Montgomery; Yusuke Nakamura; Matthias Nauck; Gerjan Navis; Ute Noethlings; Ilja M. Nolte; David J. Porteous; Anneli Pouta; Peter P. Pramstaller; Janne Pullat; Susan M. Ring; Jerome I. Rotter; Daniela Ruggiero; Aimo Ruokonen; Cinzia Sala; Nilesh J. Samani; Jennifer Sambrook; David Schlessinger; Stefan Schreiber; Heribert Schunkert; James Scott; Nicholas L. Smith; Harold Snieder; John M. Starr; Michael Stumvoll; Atsushi Takahashi; W. H. Wilson Tang; Kent Taylor; Albert Tenesa; Swee Lay Thein; Anke Toenjes; Manuela Uda; Sheila Ulivi; Dirk J. van Veldhuisen; Peter M. Visscher; Uwe Voelker; H-Erich Wichmann; Kerri L. Wiggins; Gonneke Willemsen; Tsun-Po Yang; Jing Hua Zhao; Paavo Zitting; John R. Bradley; George V. Dedoussis; Paolo Gasparini; Stanley L. Hazen; Andres Metspalu; Mario Pirastu; Alan R. Shuldiner; L. Joost van Pelt; Jaap-Jan Zwaginga; Dorret I. Boomsma; Ian J. Deary; Andre Franke; Philippe Froguel; Santhi K. Ganesh; Marjo-Riitta Jarvelin; Nicholas G. Martin; Christa Meisinger; Bruce M. Psaty; Timothy D. Spector; Nicholas J. Wareham; Jan-Willem N. Akkerman; Marina Ciullo; Panos Deloukas; Andreas Greinacher; Steve Jupe; Naoyuki Kamatani; Jyoti Khadake; Jaspal S. Kooner; Josef Penninger; Inga Prokopenko; Derek Stemple; Daniela Toniolo; Lorenz Wernisch; Serena Sanna; Andrew A. Hicks; Augusto Rendon; Manuel A. Ferreira; Willem H. Ouwehand; Nicole Soranzo

doi:10.1038/nature10659

Back

New gene functions in megakaryopoiesis and platelet formation

Journal article

Peer reviewed

New gene functions in megakaryopoiesis and platelet formation

Christian Gieger, Aparna Radhakrishnan, Ana Cvejic, Weihong Tang, Eleonora Porcu, Giorgio Pistis, Jovana Serbanovic-Canic, Ulrich Elling, Alison H. Goodall, Yann Labrune, …

Nature (London), Vol.480(7376), pp.201-208

30/11/2011

DOI: https://doi.org/10.1038/nature10659

PMCID: PMC3335296

PMID: 22139419

Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

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.

Metrics

1 Record Views

See more details

Details

Title: New gene functions in megakaryopoiesis and platelet formation
Creators - without role: Christian Gieger - Helmholtz Zentrum München
Aparna Radhakrishnan - Wellcome Sanger Institute
Ana Cvejic - Wellcome Sanger Institute
Weihong Tang - University of Minnesota
Eleonora Porcu - Institute of Genetic and Biomedical Research
Giorgio Pistis - San Raffaele University of Rome
Jovana Serbanovic-Canic - Wellcome Sanger Institute
Ulrich Elling - Austrian Academy of Sciences
Alison H. Goodall - Glenfield Hospital
Yann Labrune - Institut de Biologie de Lille
Lorna M. Lopez - University of Edinburgh
Reedik Maegi - University of Oxford
Stuart Meacham - University of Cambridge
Yukinori Okada - RIKEN Center for Integrative Medical Sciences
Nicola Pirastu - IRCCS Materno Infantile Burlo Garofolo
Rossella Sorice - Institute of Genetics and Biophysics
Alexander Teumer - University of Greifswald
Katrin Voss - NHS Blood and Transplant
Weihua Zhang - Supreme Council Of Health
Ramiro Ramirez-Solis - Wellcome Sanger Institute
Joshua C. Bis - University of Washington
David Ellinghaus - Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany
Martin Goegele - European Acad Bozen Bolzano, Ctr Biomed, I-39100 Bolzano, Italy
Jouke-Jan Hottenga - Vrije Universiteit Amsterdam
Claudia Langenberg - MRC Epidemiology Unit
Peter Kovacs - Leipzig University
Paul F. O'Reilly - Imperial College London
So-Youn Shin - Wellcome Sanger Institute
Toenu Esko - University of Tartu
Jaana Hartiala - University of Southern California
Stavroula Kanoni - Harokopio University of Athens
Federico Murgia - National Research Council
Afshin Parsa - University of Maryland, Baltimore
Jonathan Stephens - University of Cambridge
Pim van der Harst - University Medical Center Groningen
C. Ellen van der Schoot - Sanquin
Hooman Allayee - University of Southern California
Antony Attwood - University of Cambridge
Beverley Balkau - University of Paris-Sud
Francois Bastardot - University Hospital of Lausanne
Saonli Basu - University of Minnesota
Sebastian E. Baumeister - Greifswald University Hospital
Ginevra Biino - National Research Council
Lorenzo Bomba - Università Cattolica del Sacro Cuore
Amelie Bonnefond - Institut de Biologie de Lille
Francois Cambien - Sorbonne Université
John C. Chambers - Supreme Council Of Health
Francesco Cucca - Institute of Genetic and Biomedical Research
Pio D'Adamo - IRCCS Materno Infantile Burlo Garofolo
Gail Davies - University of Edinburgh
Rudolf A. de Boer - University Medical Center Groningen
Eco J. C. de Geus - Vrije Universiteit Amsterdam
Angela Doering - Helmholtz Zentrum München
Paul Elliott - Imperial College London
Jeanette Erdmann - University of Lübeck
David M. Evans - University of Bristol
Mario Falchi - Hammersmith Hospital
Wei Feng - University of Minnesota
Aaron R. Folsom - University of Minnesota
Ian H. Frazer - Princess Alexandra Hospital
Quince D. Gibson - University of Maryland, Baltimore
Nicole L. Glazer - Boston University
Chris Hammond - Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England
Anna-Liisa Hartikainen - University of Oulu
Susan R. Heckbert - University of Washington
Christian Hengstenberg - University Hospital Regensburg
Micha Hersch - SIB Swiss Institute of Bioinformatics
Thomas Illig - Helmholtz Zentrum München
Ruth J. F. Loos - MRC Epidemiology Unit
Jennifer Jolley - University of Cambridge
Kay Tee Khaw - University of Cambridge
Brigitte Kuehnel - Helmholtz Zentrum München
Marie-Christine Kyrtsonis - National and Kapodistrian University of Athens
Vasiliki Lagou - Oxford Centre for Diabetes, Endocrinology and Metabolism
Heather Lloyd-Jones - NHS Blood and Transplant
Thomas Lumley - University of Washington
Massimo Mangino - King's College London
Andrea Maschio - Institute of Genetic and Biomedical Research
Irene Mateo Leach - University of Groningen
Barbara McKnight - University of Washington
Yasin Memari - Wellcome Sanger Institute
Braxton D. Mitchell - University of Maryland, Baltimore
Grant W. Montgomery - QIMR Berghofer Medical Research Institute
Yusuke Nakamura - Tokyo University of Science
Matthias Nauck - Greifswald University Hospital
Gerjan Navis - University of Groningen
Ute Noethlings - College Station Medical Center
Ilja M. Nolte - University Medical Center Groningen
David J. Porteous - Western General Hospital
Anneli Pouta - University of Oulu
Peter P. Pramstaller - Eurac Research
Janne Pullat - University of Tartu
Susan M. Ring - University of Bristol
Jerome I. Rotter - Cedars-Sinai Medical Center
Daniela Ruggiero - Institute of Genetics and Biophysics
Aimo Ruokonen - University of Oulu
Cinzia Sala - San Raffaele University of Rome
Nilesh J. Samani - University of Leicester
Jennifer Sambrook - University of Cambridge
David Schlessinger - National Institute on Aging
Stefan Schreiber - Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany
Heribert Schunkert - University of Lübeck
James Scott - University of London
Nicholas L. Smith - University of Washington
Harold Snieder - University of Groningen
John M. Starr - University of Edinburgh
Michael Stumvoll - College Station Medical Center
Atsushi Takahashi - MED Institute
W. H. Wilson Tang - College Station Medical Center
Kent Taylor - College Station Medical Center
Albert Tenesa - College Station Medical Center
Swee Lay Thein - Kings Coll London, Dept Mol Haematol, London SE5 9NU, England
Anke Toenjes - College Station Medical Center
Manuela Uda - Cittadella Univ Monserrato, CNR, Ist Ric Genet & Biomed, I-09042 Cagliari, Italy
Sheila Ulivi - IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, I-34137 Trieste, Italy
Dirk J. van Veldhuisen - University of Groningen
Peter M. Visscher - University of Edinburgh
Uwe Voelker - University of Greifswald
H-Erich Wichmann - Helmholtz Zentrum München
Kerri L. Wiggins - University of Washington
Gonneke Willemsen - University of Amsterdam
Tsun-Po Yang - Wellcome Sanger Institute
Jing Hua Zhao - Massachusetts Rehabilitation Commission
Paavo Zitting - Lapland Cent Hosp, Dept Physiatr, Rovaniemi 96101, Finland
John R. Bradley - NIHR Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England
George V. Dedoussis - Harokopio University of Athens
Paolo Gasparini - IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, I-34137 Trieste, Italy
Stanley L. Hazen - College Station Medical Center
Andres Metspalu - University of Tartu
Mario Pirastu - CNR, Inst Populat Genet, I-07100 Sassari, Italy
Alan R. Shuldiner - Supreme Council Of Health
L. Joost van Pelt - University of Groningen
Jaap-Jan Zwaginga - Sanquin
Dorret I. Boomsma - University of Amsterdam
Ian J. Deary - University of Edinburgh
Andre Franke - Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany
Philippe Froguel - Inst Biol Lille, CNRS, UMR 8199, F-59019 Lille, France
Santhi K. Ganesh - College Station Medical Center
Marjo-Riitta Jarvelin - University of London
Nicholas G. Martin - College Station Medical Center
Christa Meisinger - Helmholtz Zentrum München
Bruce M. Psaty - University of Puget Sound
Timothy D. Spector - Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England
Nicholas J. Wareham - Massachusetts Rehabilitation Commission
Jan-Willem N. Akkerman - College Station Medical Center
Marina Ciullo - CNR, Inst Genet & Biophys A Buzzati Traverso, I-8031 Naples, Italy
Panos Deloukas - Wellcome Sanger Institute
Andreas Greinacher - University of Greifswald
Steve Jupe - EMBL European Bioinformat Inst, Prote Serv, Cambridge CB10 1SD, England
Naoyuki Kamatani - MED Institute
Jyoti Khadake - EMBL European Bioinformat Inst, Prote Serv, Cambridge CB10 1SD, England
Jaspal S. Kooner - University of London
Josef Penninger - Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria
Inga Prokopenko - University of Oxford
Derek Stemple - Wellcome Sanger Institute
Daniela Toniolo - Ist Sci San Raffaele, I-20132 Milan, Italy
Lorenz Wernisch - Biostat
Serena Sanna - Cittadella Univ Monserrato, CNR, Ist Ric Genet & Biomed, I-09042 Cagliari, Italy
Andrew A. Hicks - European Acad Bozen Bolzano, Ctr Biomed, I-39100 Bolzano, Italy
Augusto Rendon - University of Cambridge
Manuel A. Ferreira - College Station Medical Center
Willem H. Ouwehand - University of Cambridge
Nicole Soranzo - Wellcome Sanger Institute
Publication Details: Nature (London), Vol.480(7376), pp.201-208
Publisher: Springer Nature
Number of pages: 8
Grant note: P41 HG003751 / US National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA I 434 / Austrian Science Fund (FWF) CZB/4/505; ETM/55 / Chief Scientist Office WT 082597/Z/07/Z; WT 077037/Z/05/Z; WT 077047/Z/05/Z; 098051 / Wellcome Trust EBI Industry Programme BB/F019394/1 / Biotechnology and Biological Sciences Research Council; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) G0801056; G0000111; MC_U106179471; MC_U106188470; G0801056B; G0601966; G0701863; G0700704; G0401527; G0700704B; G0700931; MC_U105260799; G1000143; G0701120 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) BB/F019394/1 / BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) European Community; European Commission HEALTH-F4-2007-201413 / ENGAGE Consortium LSHG-CT-2005-518254 'ENFIN'; 215820 / EU; European Commission National Institute for Health Research, UK; National Institutes of Health Research (NIHR) G0601966; MC_U105260799; G0801056; G0700931; G0701863; G0700704; G0000111; MC_U106188470 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) RG/09/012/28096 / British Heart Foundation 226073; FP7-HEALTH-2007-223411 / EC under SLING ERC; European Research Council (ERC); European Commission
Identifiers: 9936763708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article