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; Inga Prokopenko

doi:10.1038/nature10659

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New gene functions in megakaryopoiesis and platelet formation

Journal article

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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

01/12/2011

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

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.

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Title: New gene functions in megakaryopoiesis and platelet formation
Creators: Christian Gieger - Helmholtz Zentrum München
Aparna Radhakrishnan - NHS Blood and Transplant
Ana Cvejic - NHS Blood and Transplant
Weihong Tang - University of Minnesota
Eleonora Porcu - Institute of Genetic and Biomedical Research
Giorgio Pistis - San Raffaele University of Rome
Jovana Serbanovic-Canic - University of Cambridge
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 - NHS Blood and Transplant
Yukinori Okada - RIKEN Center for Integrative Medical Sciences
Nicola Pirastu - IRCCS Materno Infantile Burlo Garofolo
Rossella Sorice - Institute of Genetics and Biophysics
Alexander Teumer - Universität Greifswald
Katrin Voss - University of Cambridge
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 - University of Amsterdam
Claudia Langenberg - MRC Epidemiology Unit
Peter Kovacs - Leipzig University
Paul F. O'Reilly - University of London
So-Youn Shin - Wellcome Sanger Institute
Toenu Esko - University of Tartu
Jaana Hartiala - University of Southern California
Stavroula Kanoni - Wellcome Sanger Institute
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 - Wellcome Sanger Institute
Beverley Balkau - Centre de recherche en Epidémiologie et Santé des Populations
Francois Bastardot - University Hospital of Lausanne
Saonli Basu - University of Minnesota
Sebastian E. Baumeister - Universitätsmedizin Greifswald
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 Burlo Garofolo, Inst Maternal & Child Hlth, I-34137 Trieste, Italy
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 - Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England
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 - NHS Blood and Transplant
Kay Tee Khaw - University of Cambridge
Brigitte Kuehnel - Helmholtz Zentrum München
Marie-Christine Kyrtsonis - National and Kapodistrian University of Athens
Vasiliki Lagou - University of Oxford
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 Medical Center Groningen
Barbara McKnight - University of Washington
Yasin Memari - King's College London
Braxton D. Mitchell - University of Maryland, Baltimore
Grant W. Montgomery - QIMR Berghofer Medical Research Institute
Yusuke Nakamura - Tokyo University of Science
Matthias Nauck - Universitätsmedizin Greifswald
Gerjan Navis - University Medical Center Groningen
Ute Noethlings - College Station Medical Center
Ilja M. Nolte - University Medical Center Groningen
David J. Porteous - University of Edinburgh
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 - Glenfield Hospital
Jennifer Sambrook - University of Cambridge
David Schlessinger - National Institute on Aging
Inga Prokopenko - School of Biosciences
Publication Details: Nature (London), Vol.480(7376), pp.201-208
Publisher: Springer Nature
Number of pages: 8
Date published: 01/12/2011
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) European Community 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) HEALTH-F4-2007-201413 / ENGAGE Consortium
Identifiers: 99928580702346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

New gene functions in megakaryopoiesis and platelet formation

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