A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-11-23

AUTHORS

Janina S. Ried, Janina Jeff M., Audrey Y. Chu, Jennifer L. Bragg-Gresham, Jenny van Dongen, Jennifer E. Huffman, Tarunveer S. Ahluwalia, Gemma Cadby, Niina Eklund, Joel Eriksson, Tõnu Esko, Mary F. Feitosa, Anuj Goel, Mathias Gorski, Caroline Hayward, Nancy L. Heard-Costa, Anne U. Jackson, Eero Jokinen, Stavroula Kanoni, Kati Kristiansson, Zoltán Kutalik, Jari Lahti, Jian'an Luan, Reedik Mägi, Anubha Mahajan, Massimo Mangino, Carolina Medina-Gomez, Keri L. Monda, Ilja M. Nolte, Louis Pérusse, Inga Prokopenko, Lu Qi, Lynda M. Rose, Erika Salvi, Megan T. Smith, Harold Snieder, Alena Stančáková, Yun Ju Sung, Ioanna Tachmazidou, Alexander Teumer, Gudmar Thorleifsson, Pim van der Harst, Ryan W. Walker, Sophie R. Wang, Sarah H. Wild, Sara M. Willems, Andrew Wong, Weihua Zhang, Eva Albrecht, Alexessander Couto Alves, Stephan J. L. Bakker, Cristina Barlassina, Traci M. Bartz, John Beilby, Claire Bellis, Richard N. Bergman, Sven Bergmann, John Blangero, Matthias Blüher, Eric Boerwinkle, Lori L. Bonnycastle, Stefan R. Bornstein, Marcel Bruinenberg, Harry Campbell, Yii-Der Ida Chen, Charleston W. K. Chiang, Peter S. Chines, Francis S Collins, Fracensco Cucca, L Adrienne Cupples, Francesca D’Avila, Eco J .C. de Geus, George Dedoussis, Maria Dimitriou, Angela Döring, Johan G. Eriksson, Aliki-Eleni Farmaki, Martin Farrall, Teresa Ferreira, Krista Fischer, Nita G. Forouhi, Nele Friedrich, Anette Prior Gjesing, Nicola Glorioso, Mariaelisa Graff, Harald Grallert, Niels Grarup, Jürgen Gräßler, Jagvir Grewal, Anders Hamsten, Marie Neergaard Harder, Catharina A. Hartman, Maija Hassinen, Nicholas Hastie, Andrew Tym Hattersley, Aki S. Havulinna, Markku Heliövaara, Hans Hillege, Albert Hofman, Oddgeir Holmen, Georg Homuth, Jouke-Jan Hottenga, Jennie Hui, Lise Lotte Husemoen, Pirro G. Hysi, Aaron Isaacs, Till Ittermann, Shapour Jalilzadeh, Alan L. James, Torben Jørgensen, Pekka Jousilahti, Antti Jula, Johanne Marie Justesen, Anne E. Justice, Mika Kähönen, Maria Karaleftheri, Kay Tee Khaw, Sirkka M. Keinanen-Kiukaanniemi, Leena Kinnunen, Paul B. Knekt, Heikki A. Koistinen, Ivana Kolcic, Ishminder K. Kooner, Seppo Koskinen, Peter Kovacs, Theodosios Kyriakou, Tomi Laitinen, Claudia Langenberg, Alexandra M. Lewin, Peter Lichtner, Cecilia M. Lindgren, Jaana Lindström, Allan Linneberg, Roberto Lorbeer, Mattias Lorentzon, Robert Luben, Valeriya Lyssenko, Satu Männistö, Paolo Manunta, Irene Mateo Leach, Wendy L. McArdle, Barbara Mcknight, Karen L. Mohlke, Evelin Mihailov, Lili Milani, Rebecca Mills, May E. Montasser, Andrew P. Morris, Gabriele Müller, Arthur W. Musk, Narisu Narisu, Ken K. Ong, Ben A. Oostra, Clive Osmond, Aarno Palotie, James S. Pankow, Lavinia Paternoster, Brenda W. Penninx, Irene Pichler, Maria G. Pilia, Ozren Polašek, Peter P. Pramstaller, Olli T Raitakari, Tuomo Rankinen, D. C. Rao, Nigel W. Rayner, Rasmus Ribel-Madsen, Treva K. Rice, Marcus Richards, Paul M. Ridker, Fernando Rivadeneira, Kathy A. Ryan, Serena Sanna, Mark A. Sarzynski, Salome Scholtens, Robert A. Scott, Sylvain Sebert, Lorraine Southam, Thomas Hempel Sparsø, Valgerdur Steinthorsdottir, Kathleen Stirrups, Ronald P. Stolk, Konstantin Strauch, Heather M. Stringham, Morris A. Swertz, Amy J. Swift, Anke Tönjes, Emmanouil Tsafantakis, Peter J. van der Most, Jana V. Van Vliet-Ostaptchouk, Liesbeth Vandenput, Erkki Vartiainen, Cristina Venturini, Niek Verweij, Jorma S. Viikari, Veronique Vitart, Marie-Claude Vohl, Judith M. Vonk, Gérard Waeber, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Thomas W. Winkler, Alan F. Wright, Laura M. Yerges-Armstrong, Jing Hua Zhao, M. Carola Zillikens, Dorret I. Boomsma, Claude Bouchard, John C. Chambers, Daniel I. Chasman, Daniele Cusi, Ron T. Gansevoort, Christian Gieger, Torben Hansen, Andrew A. Hicks, Frank Hu, Kristian Hveem, Marjo-Riitta Jarvelin, Eero Kajantie, Jaspal S. Kooner, Diana Kuh, Johanna Kuusisto, Markku Laakso, Timo A. Lakka, Terho Lehtimäki, Andres Metspalu, Inger Njølstad, Claes Ohlsson, Albertine J. Oldehinkel, Lyle J. Palmer, Oluf Pedersen, Markus Perola, Annette Peters, Bruce M. Psaty, Hannu Puolijoki, Rainer Rauramaa, Igor Rudan, Veikko Salomaa, Peter E. H. Schwarz, Alan R. Shudiner, Jan H. Smit, Thorkild I. A. Sørensen, Timothy D. Spector, Kari Stefansson, Michael Stumvoll, Angelo Tremblay, Jaakko Tuomilehto, André G. Uitterlinden, Matti Uusitupa, Uwe Völker, Peter Vollenweider, Nicholas J. Wareham, Hugh Watkins, James F. Wilson, Eleftheria Zeggini, Goncalo R. Abecasis, Michael Boehnke, Ingrid B. Borecki, Panos Deloukas, Cornelia M. van Duijn, Caroline Fox, Leif C. Groop, Iris M. Heid, David J. Hunter, Robert C. Kaplan, Mark I. McCarthy, Kari E. North, Jeffrey R. O'Connell, David Schlessinger, Unnur Thorsteinsdottir, David P. Strachan, Timothy Frayling, Joel N. Hirschhorn, Martina Müller-Nurasyid, Ruth J. F. Loos

ABSTRACT

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways. More... »

PAGES

13357

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    N/A

    VOLUME

    7

    Author Affiliations

  • Icahn School of Medicine at Mount Sinai
  • Brigham and Women's Hospital
  • University of Michigan–Ann Arbor
  • VU University Amsterdam
  • University of Edinburgh
  • Steno Diabetes Center
  • University of Western Australia
  • National Institute for Health and Welfare
  • University of Gothenburg
  • Harvard University
  • Washington University in St. Louis
  • Wellcome Centre for Human Genetics
  • University of Regensburg
  • Boston University School of Medicine
  • University of Helsinki
  • Queen Mary University of London
  • Institute of Social and Preventive Medicine
  • Institute of Metabolic Science
  • King's College London
  • Erasmus University Medical Center
  • Amgen (United States)
  • University Medical Center Groningen
  • Université Laval
  • University of Oxford
  • Fondazione Filarete
  • University of Washington
  • Wellcome Sanger Institute
  • University of Greifswald
  • deCODE Genetics (Iceland)
  • Boston Children's Hospital
  • MRC Unit for Lifelong Health and Ageing
  • Ealing Hospital NHS Trust
  • Imperial College London
  • Genome Institute of Singapore
  • University of Southern California
  • University of Lausanne
  • The University of Texas Rio Grande Valley
  • Leipzig University
  • The University of Texas Health Science Center at Houston
  • National Human Genome Research Institute
  • TU Dresden
  • Harbor–UCLA Medical Center
  • University of California Los Angeles
  • University of Sassari
  • National Heart Lung and Blood Institute
  • EMGO Institute for Health and Care Research
  • Harokopio University
  • University of Tartu
  • University of Copenhagen
  • University of North Carolina at Chapel Hill
  • German Center for Diabetes Research
  • Karolinska University Hospital
  • Kuopion Liikuntalääketieteen Tutkimuslaitos
  • University of Exeter
  • Norwegian University of Science and Technology
  • Rigshospitalet
  • Sir Charles Gairdner Hospital
  • Research Centre for Prevention and Health
  • University of Tampere
  • Oulu University Hospital
  • Minerva Foundation
  • University of Split
  • University of Eastern Finland
  • University College London
  • University of Cambridge
  • Lund University
  • San Raffaele Hospital
  • University of Bristol
  • Fred Hutchinson Cancer Research Center
  • University of Maryland, Baltimore
  • University of Liverpool
  • Massachusetts General Hospital
  • University of Minnesota
  • VU University Medical Center
  • University of Lübeck
  • Institute of Genetic and Biomedical Research
  • Ospedale di Bolzano
  • University of Turku
  • Pennington Biomedical Research Center
  • University of Oulu
  • Ludwig Maximilian University of Munich
  • Turku University Hospital
  • The Arctic University of Norway
  • Imperial College Healthcare NHS Trust
  • University of Southern Denmark
  • University of Adelaide
  • German Centre for Cardiovascular Research
  • Seinäjoen Keskussairaala
  • Kuopio University Hospital
  • Baltimore VA Medical Center
  • Frederiksberg Hospital
  • University of Iceland
  • King Abdulaziz University
  • Helmholtz Zentrum München
  • Albert Einstein College of Medicine
  • NIHR Oxford Musculoskeletal Biomedical Research Unit
  • National Institute on Aging
  • Broad Institute
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms13357

    DOI

    http://dx.doi.org/10.1038/ncomms13357

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1033596245

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27876822


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    61 schema:description Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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