IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_s41467-017-00108-3.html
   My bibliography  Save this article

Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

Author

Listed:
  • Carolina Medina-Gomez

    (Erasmus MC University
    The Generation R Study Group, Erasmus Medical Center
    Erasmus Medical Center)

  • John P. Kemp

    (University of Queensland Diamantina Institute, Translational Research Institute
    MRC Integrative Epidemiology Unit, University of Bristol)

  • Niki L. Dimou

    (Department of Computer Science and Biomedical Informatics of the University of Thessaly
    University of Ioannina Medical School)

  • Eskil Kreiner

    (University of Copenhagen)

  • Alessandra Chesi

    (Children’s Hospital of Philadelphia)

  • Babette S. Zemel

    (Children’s Hospital of Philadelphia
    University of Pennsylvania)

  • Klaus Bønnelykke

    (University of Copenhagen)

  • Cindy G. Boer

    (Erasmus MC University)

  • Tarunveer S. Ahluwalia

    (University of Copenhagen
    Steno Diabetes Center Copenhagen)

  • Hans Bisgaard

    (University of Copenhagen)

  • Evangelos Evangelou

    (University of Ioannina Medical School
    School of Public Health, Imperial College London)

  • Denise H. M. Heppe

    (The Generation R Study Group, Erasmus Medical Center
    Erasmus Medical Center)

  • Lynda F. Bonewald

    (School of Medicine, Indiana University)

  • Jeffrey P. Gorski

    (University of Missouri-Kansas City)

  • Mohsen Ghanbari

    (Erasmus Medical Center
    Mashhad University of Medical Sciences)

  • Serkalem Demissie

    (Boston University School of Public Health)

  • Gustavo Duque

    (The University of Melbourne and Western Health)

  • Matthew T. Maurano

    (New York University Langone Medical Center)

  • Douglas P. Kiel

    (Hebrew SeniorLife, Institute for Aging Research
    Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Yi-Hsiang Hsu

    (Hebrew SeniorLife, Institute for Aging Research
    Broad Institute of MIT and Harvard
    Harvard School of Public Health)

  • Bram van der Eerden

    (Erasmus MC University)

  • Cheryl Ackert-Bicknell

    (University of Rochester)

  • Sjur Reppe

    (Oslo University Hospital
    Unger-Vetlesen Institute, Oslo Diakonale Hospital)

  • Kaare M. Gautvik

    (Unger-Vetlesen Institute, Oslo Diakonale Hospital
    University of Oslo)

  • Truls Raastad

    (Norwegian School of Sports Sciences)

  • David Karasik

    (Hebrew SeniorLife, Institute for Aging Research
    Bar-Ilan University)

  • Jeroen van de Peppel

    (Erasmus MC University)

  • Vincent W. V. Jaddoe

    (The Generation R Study Group, Erasmus Medical Center)

  • André G. Uitterlinden

    (Erasmus MC University
    The Generation R Study Group, Erasmus Medical Center
    Erasmus Medical Center)

  • Jonathan H. Tobias

    (University of Bristol)

  • Struan F.A. Grant

    (Children’s Hospital of Philadelphia
    University of Pennsylvania
    The Children’s Hospital of Philadelphia)

  • Pantelis G. Bagos

    (Department of Computer Science and Biomedical Informatics of the University of Thessaly)

  • David M. Evans

    (University of Queensland Diamantina Institute, Translational Research Institute
    MRC Integrative Epidemiology Unit, University of Bristol)

  • Fernando Rivadeneira

    (Erasmus MC University
    The Generation R Study Group, Erasmus Medical Center
    Erasmus Medical Center)

Abstract

Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34–52%) for TBLH-BMD, and 39% (95% CI: 30–48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29–56%). We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.

Suggested Citation

  • Carolina Medina-Gomez & John P. Kemp & Niki L. Dimou & Eskil Kreiner & Alessandra Chesi & Babette S. Zemel & Klaus Bønnelykke & Cindy G. Boer & Tarunveer S. Ahluwalia & Hans Bisgaard & Evangelos Evang, 2017. "Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00108-3
    DOI: 10.1038/s41467-017-00108-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-00108-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-00108-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00108-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.