Defining the role of common variation in the genomic and biological architecture of adult human height View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-11

AUTHORS

Andrew R Wood, Tonu Esko, Jian Yang, Sailaja Vedantam, Tune H Pers, Stefan Gustafsson, Audrey Y Chu, Karol Estrada, Jian’an Luan, Zoltán Kutalik, Najaf Amin, Martin L Buchkovich, Damien C Croteau-Chonka, Felix R Day, Yanan Duan, Tove Fall, Rudolf Fehrmann, Teresa Ferreira, Anne U Jackson, Juha Karjalainen, Ken Sin Lo, Adam E Locke, Reedik Mägi, Evelin Mihailov, Eleonora Porcu, Joshua C Randall, André Scherag, Anna AE Vinkhuyzen, Harm-Jan Westra, Thomas W Winkler, Tsegaselassie Workalemahu, Jing Hua Zhao, Devin Absher, Eva Albrecht, Denise Anderson, Jeffrey Baron, Marian Beekman, Ayse Demirkan, Georg B Ehret, Bjarke Feenstra, Mary F Feitosa, Krista Fischer, Ross M Fraser, Anuj Goel, Jian Gong, Anne E Justice, Stavroula Kanoni, Marcus E Kleber, Kati Kristiansson, Unhee Lim, Vaneet Lotay, Julian C Lui, Massimo Mangino, Irene Mateo Leach, Carolina Medina-Gomez, Michael A Nalls, Dale R Nyholt, Cameron D Palmer, Dorota Pasko, Sonali Pechlivanis, Inga Prokopenko, Janina S Ried, Stephan Ripke, Dmitry Shungin, Alena Stancáková, Rona J Strawbridge, Yun Ju Sung, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sander W van der Laan, Jessica van Setten, Jana V Van Vliet-Ostaptchouk, Zhaoming Wang, Loïc Yengo, Weihua Zhang, Uzma Afzal, Johan Ärnlöv, Gillian M Arscott, Stefania Bandinelli, Amy Barrett, Claire Bellis, Amanda J Bennett, Christian Berne, Matthias Blüher, Jennifer L Bolton, Yvonne Böttcher, Heather A Boyd, Marcel Bruinenberg, Brendan M Buckley, Steven Buyske, Ida H Caspersen, Peter S Chines, Robert Clarke, Simone Claudi-Boehm, Matthew Cooper, E Warwick Daw, Pim A De Jong, Joris Deelen, Graciela Delgado, Josh C Denny, Rosalie Dhonukshe-Rutten, Maria Dimitriou, Alex SF Doney, Marcus Dörr, Niina Eklund, Elodie Eury, Lasse Folkersen, Melissa E Garcia, Frank Geller, Vilmantas Giedraitis, Alan S Go, Harald Grallert, Tanja B Grammer, Jürgen Gräßler, Henrik Grönberg, Lisette C.P.G.M. de Groot, Christopher J Groves, Jeffrey Haessler, Per Hall, Toomas Haller, Goran Hallmans, Anke Hannemann, Catharina A Hartman, Maija Hassinen, Caroline Hayward, Nancy L Heard-Costa, Quinta Helmer, Gibran Hemani, Anjali K Henders, Hans L Hillege, Mark A Hlatky, Wolfgang Hoffmann, Per Hoffmann, Oddgeir Holmen, Jeanine J Houwing-Duistermaat, Thomas Illig, Aaron Isaacs, Alan L James, Janina Jeff, Berit Johansen, Åsa Johansson, Jennifer Jolley, Thorhildur Juliusdottir, Juhani Junttila, Abel N Kho, Leena Kinnunen, Norman Klopp, Thomas Kocher, Wolfgang Kratzer, Peter Lichtner, Lars Lind, Jaana Lindström, Stéphane Lobbens, Mattias Lorentzon, Yingchang Lu, Valeriya Lyssenko, Patrik KE Magnusson, Anubha Mahajan, Marc Maillard, Wendy L McArdle, Colin A McKenzie, Stela McLachlan, Paul J McLaren, Cristina Menni, Sigrun Merger, Lili Milani, Alireza Moayyeri, Keri L Monda, Mario A Morken, Gabriele Müller, Martina Müller-Nurasyid, Arthur W Musk, Narisu Narisu, Matthias Nauck, Ilja M Nolte, Markus M Nöthen, Laticia Oozageer, Stefan Pilz, Nigel W Rayner, Frida Renstrom, Neil R Robertson, Lynda M Rose, Ronan Roussel, Serena Sanna, Hubert Scharnagl, Salome Scholtens, Fredrick R Schumacher, Heribert Schunkert, Robert A Scott, Joban Sehmi, Thomas Seufferlein, Jianxin Shi, Karri Silventoinen, Johannes H Smit, Albert Vernon Smith, Joanna Smolonska, Alice V Stanton, Kathleen Stirrups, David J Stott, Heather M Stringham, Johan Sundström, Morris A Swertz, Ann-Christine Syvänen, Bamidele O Tayo, Gudmar Thorleifsson, Jonathan P Tyrer, Suzanne van Dijk, Natasja M van Schoor, Nathalie van der Velde, Diana van Heemst, Floor VA van Oort, Sita H Vermeulen, Niek Verweij, Judith M Vonk, Lindsay L Waite, Melanie Waldenberger, Roman Wennauer, Lynne R Wilkens, Christina Willenborg, Tom Wilsgaard, Mary K Wojczynski, Andrew Wong, Alan F Wright, Qunyuan Zhang, Dominique Arveiler, Stephan JL Bakker, John Beilby, Richard N Bergman, Sven Bergmann, Reiner Biffar, John Blangero, Dorret I Boomsma, Stefan R Bornstein, Pascal Bovet, Paolo Brambilla, Morris J Brown, Harry Campbell, Mark J Caulfield, Aravinda Chakravarti, Rory Collins, Francis S Collins, Dana C Crawford, L Adrienne Cupples, John Danesh, Ulf de Faire, Hester M den Ruijter, Raimund Erbel, Jeanette Erdmann, Johan G Eriksson, Martin Farrall, Ele Ferrannini, Jean Ferrières, Ian Ford, Nita G Forouhi, Terrence Forrester, Ron T Gansevoort, Pablo V Gejman, Christian Gieger, Alain Golay, Omri Gottesman, Vilmundur Gudnason, Ulf Gyllensten, David W Haas, Alistair S Hall, Tamara B Harris, Andrew T Hattersley, Andrew C Heath, Christian Hengstenberg, Andrew A Hicks, Lucia A Hindorff, Aroon D Hingorani, Albert Hofman, G Kees Hovingh, Steve E Humphries, Steven C Hunt, Elina Hypponen, Kevin B Jacobs, Marjo-Riitta Jarvelin, Pekka Jousilahti, Antti M Jula, Jaakko Kaprio, John JP Kastelein, Manfred Kayser, Frank Kee, Sirkka M Keinanen-Kiukaanniemi, Lambertus A Kiemeney, Jaspal S Kooner, Charles Kooperberg, Seppo Koskinen, Peter Kovacs, Aldi T Kraja, Meena Kumari, Johanna Kuusisto, Timo A Lakka, Claudia Langenberg, Loic Le Marchand, Terho Lehtimäki, Sara Lupoli, Pamela AF Madden, Satu Männistö, Paolo Manunta, André Marette, Tara C Matise, Barbara McKnight, Thomas Meitinger, Frans L Moll, Grant W Montgomery, Andrew D Morris, Andrew P Morris, Jeffrey C Murray, Mari Nelis, Claes Ohlsson, Albertine J Oldehinkel, Ken K Ong, Willem H Ouwehand, Gerard Pasterkamp, Annette Peters, Peter P Pramstaller, Jackie F Price, Lu Qi, Olli T Raitakari, Tuomo Rankinen, DC Rao, Treva K Rice, Marylyn Ritchie, Igor Rudan, Veikko Salomaa, Nilesh J Samani, Jouko Saramies, Mark A Sarzynski, Peter EH Schwarz, Sylvain Sebert, Peter Sever, Alan R Shuldiner, Juha Sinisalo, Valgerdur Steinthorsdottir, Ronald P Stolk, Jean-Claude Tardif, Anke Tönjes, Angelo Tremblay, Elena Tremoli, Jarmo Virtamo, Marie-Claude Vohl, , , , , Philippe Amouyel, Folkert W Asselbergs, Themistocles L Assimes, Murielle Bochud, Bernhard O Boehm, Eric Boerwinkle, Erwin P Bottinger, Claude Bouchard, Stéphane Cauchi, John C Chambers, Stephen J Chanock, Richard S Cooper, Paul IW de Bakker, George Dedoussis, Luigi Ferrucci, Paul W Franks, Philippe Froguel, Leif C Groop, Christopher A Haiman, Anders Hamsten, M Geoffrey Hayes, Jennie Hui, David J. Hunter, Kristian Hveem, J Wouter Jukema, Robert C Kaplan, Mika Kivimaki, Diana Kuh, Markku Laakso, Yongmei Liu, Nicholas G Martin, Winfried März, Mads Melbye, Susanne Moebus, Patricia B Munroe, Inger Njølstad, Ben A Oostra, Colin NA Palmer, Nancy L Pedersen, Markus Perola, Louis Pérusse, Ulrike Peters, Joseph E Powell, Chris Power, Thomas Quertermous, Rainer Rauramaa, Eva Reinmaa, Paul M Ridker, Fernando Rivadeneira, Jerome I Rotter, Timo E Saaristo, Danish Saleheen, David Schlessinger, P Eline Slagboom, Harold Snieder, Tim D Spector, Konstantin Strauch, Michael Stumvoll, Jaakko Tuomilehto, Matti Uusitupa, Pim van der Harst, Henry Völzke, Mark Walker, Nicholas J Wareham, Hugh Watkins, H-Erich Wichmann, James F Wilson, Pieter Zanen, Panos Deloukas, Iris M Heid, Cecilia M Lindgren, Karen L Mohlke, Elizabeth K Speliotes, Unnur Thorsteinsdottir, Inês Barroso, Caroline S Fox, Kari E North, David P Strachan, Jacques S. Beckmann, Sonja I Berndt, Michael Boehnke, Ingrid B Borecki, Mark I McCarthy, Andres Metspalu, Kari Stefansson, André G Uitterlinden, Cornelia M van Duijn, Lude Franke, Cristen J Willer, Alkes L. Price, Guillaume Lettre, Ruth JF Loos, Michael N Weedon, Erik Ingelsson, Jeffrey R O’Connell, Goncalo R Abecasis, Daniel I Chasman, Michael E Goddard, Peter M Visscher, Joel N Hirschhorn, Timothy M Frayling

ABSTRACT

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants. More... »

PAGES

1173-1186

References to SciGraph publications

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    11

    VOLUME

    46

    Author Affiliations

  • University of Exeter
  • Harvard University
  • University of Queensland
  • Broad Institute
  • Technical University of Denmark
  • Uppsala University
  • Brigham and Women's Hospital
  • Massachusetts General Hospital
  • Institute of Metabolic Science
  • University of Lausanne
  • Erasmus University Medical Center
  • University of North Carolina at Chapel Hill
  • Washington University in St. Louis
  • Karolinska Institute
  • Wellcome Centre for Human Genetics
  • University of Michigan–Ann Arbor
  • Montreal Heart Institute
  • University of Tartu
  • Institute of Genetic and Biomedical Research
  • Wellcome Sanger Institute
  • Jena University Hospital
  • University of Regensburg
  • HudsonAlpha Institute for Biotechnology
  • Helmholtz Zentrum München
  • National Institutes of Health
  • Leiden University Medical Center
  • University Hospital of Geneva
  • Statens Serum Institut
  • University of Edinburgh
  • University of Oxford
  • Fred Hutchinson Cancer Research Center
  • University Hospital Ulm
  • National Institute for Health and Welfare
  • University of Hawaii at Manoa
  • Icahn School of Medicine at Mount Sinai
  • King's College London
  • QIMR Berghofer Medical Research Institute
  • Essen University Hospital
  • Imperial College London
  • Umeå University
  • University of Eastern Finland
  • National Institute on Aging
  • University of Greifswald
  • University Medical Center Utrecht
  • University Medical Center Groningen
  • Leidos (United States)
  • Université Lille 2 Droit et Santé
  • Dalarna University
  • Pathwest Laboratory Medicine
  • Azienda Sanitaria di Firenze
  • Texas Biomedical Research Institute
  • Leipzig University
  • University College Cork
  • Rutgers University
  • Norwegian University of Science and Technology
  • Heidelberg University
  • Vanderbilt University
  • Wageningen University & Research
  • Harokopio University
  • University of Helsinki
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • Kaiser Permanente
  • German Center for Diabetes Research
  • Kuopion Liikuntalääketieteen Tutkimuslaitos
  • Boston University School of Medicine
  • VU University Amsterdam
  • Stanford University
  • University of Bonn
  • Hannover Medical School
  • University of Western Australia
  • NHS Blood and Transplant
  • University of Oulu
  • Northwestern University
  • University of Ulm
  • University of Gothenburg
  • Steno Diabetes Center
  • University Hospital of Lausanne
  • University of Bristol
  • University of the West Indies
  • Amgen (United States)
  • German Centre for Cardiovascular Research
  • Sir Charles Gairdner Hospital
  • Ealing Hospital NHS Trust
  • Medical University of Graz
  • Lund University
  • Paris Diderot University
  • University of Southern California
  • Technical University Munich
  • National Cancer Institute
  • University of Iceland
  • Royal College of Surgeons in Ireland
  • University of Glasgow
  • Loyola University Chicago
  • deCODE Genetics (Iceland)
  • University of Cambridge
  • EMGO Institute for Health and Care Research
  • Academic Medical Center
  • Radboud University Nijmegen Medical Centre
  • University of Lübeck
  • The Arctic University of Norway
  • MRC Unit for Lifelong Health and Ageing
  • University of Strasbourg
  • Ministry of Health
  • University of Milan
  • Queen Mary University of London
  • Johns Hopkins University
  • Boston University
  • Helsinki University Central Hospital
  • University of Pisa
  • Hôpital Rangueil
  • NorthShore University HealthSystem
  • University of Leeds
  • National Human Genome Research Institute
  • University College London
  • University of Utah
  • Queen's University Belfast
  • Oulu University Hospital
  • University of Tampere
  • Fondazione Filarete
  • Vita-Salute San Raffaele University
  • Université Laval
  • University of Washington
  • University of Liverpool
  • University of Iowa
  • Ospedale di Bolzano
  • University of Turku
  • Pennington Biomedical Research Center
  • Pennsylvania State University
  • University of Split
  • Glenfield Hospital
  • South Karelia Central Hospital
  • Baltimore VA Medical Center
  • University of Montreal
  • Istituti di Ricovero e Cura a Carattere Scientifico
  • Nanyang Technological University
  • The University of Texas Health Science Center at Houston
  • Imperial College Healthcare NHS Trust
  • University of South Australia
  • Netherlands Heart Institute
  • Albert Einstein College of Medicine
  • Wake Forest University
  • Synlab (Germany)
  • Harbor–UCLA Medical Center
  • Pirkanmaa Hospital District
  • University of Pennsylvania
  • Ludwig Maximilian University of Munich
  • Danube University Krems
  • Kuopio University Hospital
  • Newcastle University
  • King Abdulaziz University
  • National Heart Lung and Blood Institute
  • NIHR Oxford Musculoskeletal Biomedical Research Unit
  • University of Maryland, Baltimore
  • University of Melbourne
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3097

    DOI

    http://dx.doi.org/10.1038/ng.3097

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1006357119

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25282103


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