Large meta-analysis of genome-wide association studies identifies five loci for lean body mass View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

M. Carola Zillikens, Serkalem Demissie, Yi-Hsiang Hsu, Laura M. Yerges-Armstrong, Wen-Chi Chou, Lisette Stolk, Gregory Livshits, Linda Broer, Toby Johnson, Daniel L. Koller, Zoltán Kutalik, Jian’an Luan, Ida Malkin, Janina S. Ried, Albert V. Smith, Gudmar Thorleifsson, Liesbeth Vandenput, Jing Hua Zhao, Weihua Zhang, Ali Aghdassi, Kristina Åkesson, Najaf Amin, Leslie J. Baier, Inês Barroso, David A. Bennett, Lars Bertram, Rainer Biffar, Murielle Bochud, Michael Boehnke, Ingrid B. Borecki, Aron S. Buchman, Liisa Byberg, Harry Campbell, Natalia Campos Obanda, Jane A. Cauley, Peggy M. Cawthon, Henna Cederberg, Zhao Chen, Nam H. Cho, Hyung Jin Choi, Melina Claussnitzer, Francis Collins, Steven R. Cummings, Philip L. De Jager, Ilja Demuth, Rosalie A. M. Dhonukshe-Rutten, Luda Diatchenko, Gudny Eiriksdottir, Anke W. Enneman, Mike Erdos, Johan G. Eriksson, Joel Eriksson, Karol Estrada, Daniel S. Evans, Mary F. Feitosa, Mao Fu, Melissa Garcia, Christian Gieger, Thomas Girke, Nicole L. Glazer, Harald Grallert, Jagvir Grewal, Bok-Ghee Han, Robert L. Hanson, Caroline Hayward, Albert Hofman, Eric P. Hoffman, Georg Homuth, Wen-Chi Hsueh, Monica J. Hubal, Alan Hubbard, Kim M. Huffman, Lise B. Husted, Thomas Illig, Erik Ingelsson, Till Ittermann, John-Olov Jansson, Joanne M. Jordan, Antti Jula, Magnus Karlsson, Kay-Tee Khaw, Tuomas O. Kilpeläinen, Norman Klopp, Jacqueline S. L. Kloth, Heikki A. Koistinen, William E. Kraus, Stephen Kritchevsky, Teemu Kuulasmaa, Johanna Kuusisto, Markku Laakso, Jari Lahti, Thomas Lang, Bente L. Langdahl, Lenore J. Launer, Jong-Young Lee, Markus M. Lerch, Joshua R. Lewis, Lars Lind, Cecilia Lindgren, Yongmei Liu, Tian Liu, Youfang Liu, Östen Ljunggren, Mattias Lorentzon, Robert N. Luben, William Maixner, Fiona E. McGuigan, Carolina Medina-Gomez, Thomas Meitinger, Håkan Melhus, Dan Mellström, Simon Melov, Karl Michaëlsson, Braxton D. Mitchell, Andrew P. Morris, Leif Mosekilde, Anne Newman, Carrie M. Nielson, Jeffrey R. O’Connell, Ben A. Oostra, Eric S. Orwoll, Aarno Palotie, Stephen C. J. Parker, Munro Peacock, Markus Perola, Annette Peters, Ozren Polasek, Richard L. Prince, Katri Räikkönen, Stuart H. Ralston, Samuli Ripatti, John A. Robbins, Jerome I. Rotter, Igor Rudan, Veikko Salomaa, Suzanne Satterfield, Eric E. Schadt, Sabine Schipf, Laura Scott, Joban Sehmi, Jian Shen, Chan Soo Shin, Gunnar Sigurdsson, Shad Smith, Nicole Soranzo, Alena Stančáková, Elisabeth Steinhagen-Thiessen, Elizabeth A. Streeten, Unnur Styrkarsdottir, Karin M. A. Swart, Sian-Tsung Tan, Mark A. Tarnopolsky, Patricia Thompson, Cynthia A. Thomson, Unnur Thorsteinsdottir, Emmi Tikkanen, Gregory J. Tranah, Jaakko Tuomilehto, Natasja M. van Schoor, Arjun Verma, Peter Vollenweider, Henry Völzke, Jean Wactawski-Wende, Mark Walker, Michael N. Weedon, Ryan Welch, H.-Erich Wichmann, Elisabeth Widen, Frances M. K. Williams, James F. Wilson, Nicole C. Wright, Weijia Xie, Lei Yu, Yanhua Zhou, John C. Chambers, Angela Döring, Cornelia M. van Duijn, Michael J. Econs, Vilmundur Gudnason, Jaspal S. Kooner, Bruce M. Psaty, Timothy D. Spector, Kari Stefansson, Fernando Rivadeneira, André G. Uitterlinden, Nicholas J. Wareham, Vicky Ossowski, Dawn Waterworth, Ruth J. F. Loos, David Karasik, Tamara B. Harris, Claes Ohlsson, Douglas P. Kiel

ABSTRACT

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10-8) or suggestively genome wide (p < 2.3 × 10-6). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated. More... »

PAGES

80

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    8

    Author Affiliations

  • Erasmus University Medical Center
  • Boston University
  • Harvard University
  • University of Maryland, Baltimore
  • Broad Institute
  • King's College London
  • Swiss Institute of Bioinformatics
  • Indiana University – Purdue University Indianapolis
  • University of Cambridge
  • Tel Aviv University
  • University of Iceland
  • University of Gothenburg
  • Ealing Hospital NHS Trust
  • University of Greifswald
  • Skåne University Hospital
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • Institute of Metabolic Science
  • Rush University Medical Center
  • Imperial College London
  • University of Michigan–Ann Arbor
  • Washington University in St. Louis
  • Uppsala University
  • University of Edinburgh
  • University of Pittsburgh
  • California Pacific Medical Center
  • University of Arizona
  • Ajou University
  • Chungbuk National University Hospital
  • Beth Israel Deaconess Medical Center
  • National Human Genome Research Institute
  • Charité
  • Wageningen University & Research
  • University of North Carolina at Chapel Hill
  • Icelandic Heart Association
  • National Institute for Health and Welfare
  • National Institutes of Health
  • Helmholtz Zentrum München
  • University of California, Riverside
  • Korea National Institute of Health
  • Binghamton University
  • Children’s National Health System
  • University of California, Berkeley
  • Duke University
  • Aarhus University Hospital
  • Hannover Medical School
  • Stanford University
  • Lund University
  • Icahn School of Medicine at Mount Sinai
  • Minerva Foundation
  • Wake Forest University
  • University of Helsinki
  • University of California, San Francisco
  • University of Sydney
  • Wellcome Centre for Human Genetics
  • Max Planck Institute for Human Development
  • Technical University Munich
  • University of Southern California
  • Baltimore VA Medical Center
  • University of Liverpool
  • Oregon Health & Science University
  • Centre for Medical Systems Biology
  • University of Tartu
  • University of Split
  • University of Western Australia
  • Western General Hospital
  • Wellcome Sanger Institute
  • University of California, Davis
  • Harbor–UCLA Medical Center
  • University of Tennessee Health Science Center
  • Seoul National University
  • National University Hospital of Iceland
  • Duke University Hospital
  • EMGO Institute for Health and Care Research
  • McMaster University Medical Centre
  • Stony Brook University
  • Dasman Diabetes Institute
  • University Hospital of Lausanne
  • University at Buffalo, State University of New York
  • Newcastle University
  • University of Exeter
  • University of Alabama at Birmingham
  • Imperial College Healthcare NHS Trust
  • PricewaterhouseCoopers (United States)
  • GlaxoSmithKline (United States)
  • Bar-Ilan University
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-017-00031-7

    DOI

    http://dx.doi.org/10.1038/s41467-017-00031-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1090696177

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28724990


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