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GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures

Author

Listed:
  • Unnur Styrkarsdottir

    (deCODE genetics/Amgen Inc.)

  • Olafur A. Stefansson

    (deCODE genetics/Amgen Inc.)

  • Kristbjorg Gunnarsdottir

    (deCODE genetics/Amgen Inc.)

  • Gudmar Thorleifsson

    (deCODE genetics/Amgen Inc.)

  • Sigrun H. Lund

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Lilja Stefansdottir

    (deCODE genetics/Amgen Inc.)

  • Kristinn Juliusson

    (deCODE genetics/Amgen Inc.)

  • Arna B. Agustsdottir

    (deCODE genetics/Amgen Inc.)

  • Florian Zink

    (deCODE genetics/Amgen Inc.)

  • Gisli H. Halldorsson

    (deCODE genetics/Amgen Inc.)

  • Erna V. Ivarsdottir

    (deCODE genetics/Amgen Inc.)

  • Stefania Benonisdottir

    (deCODE genetics/Amgen Inc.)

  • Hakon Jonsson

    (deCODE genetics/Amgen Inc.)

  • Arnaldur Gylfason

    (deCODE genetics/Amgen Inc.)

  • Kristjan Norland

    (deCODE genetics/Amgen Inc.)

  • Katerina Trajanoska

    (ErasmusMC
    ErasmusMC)

  • Cindy G. Boer

    (ErasmusMC)

  • Lorraine Southam

    (Wellcome Trust Sanger Institute
    University of Oxford)

  • Jason C. S. Leung

    (The Chinese University of Hong Kong)

  • Nelson L. S. Tang

    (The Chinese University of Hong Kong
    CUHK Shenzhen Research Institute)

  • Timothy C. Y. Kwok

    (The Chinese University of Hong Kong
    Prince of Wales Hospital)

  • Jenny S. W. Lee

    (The Chinese University of Hong Kong
    Alice Ho Miu Ling Nethersole Hospital and Tai Po Hospital)

  • Suzanne C. Ho

    (The Chinese University of Hong Kong)

  • Inger Byrjalsen

    (Nordic Bioscience A/S)

  • Jacqueline R. Center

    (Garvan Institute of Medical Research
    University of Notre Dame Australia
    University of New South Wales)

  • Seung Hun Lee

    (University of Ulsan College of Medicine)

  • Jung-Min Koh

    (University of Ulsan College of Medicine)

  • L. Stefan Lohmander

    (Lund University)

  • Lan T. Ho-Pham

    (Ton Duc Thang University)

  • Tuan V. Nguyen

    (Garvan Institute of Medical Research
    University of New South Wales
    University of Technology Sydney)

  • John A. Eisman

    (Garvan Institute of Medical Research
    University of Notre Dame Australia
    University of New South Wales
    Garvan Institute of Medical Research)

  • Jean Woo

    (The Chinese University of Hong Kong)

  • Ping-C. Leung

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • John Loughlin

    (Newcastle University)

  • Eleftheria Zeggini

    (Wellcome Trust Sanger Institute
    Institute of Translational Genomics, Helmholtz Zentrum München)

  • Claus Christiansen

    (Nordic Bioscience A/S)

  • Fernando Rivadeneira

    (ErasmusMC
    ErasmusMC)

  • Joyce Meurs

    (ErasmusMC)

  • Andre G. Uitterlinden

    (ErasmusMC)

  • Brynjolfur Mogensen

    (University of Iceland
    The National University Hospital of Iceland
    The National University Hospital of Iceland, and University of Iceland)

  • Helgi Jonsson

    (University of Iceland
    Landspitali–The National University Hospital of Iceland)

  • Thorvaldur Ingvarsson

    (University of Iceland
    Akureyri Hospital
    University of Akureyri)

  • Gunnar Sigurdsson

    (University of Iceland
    Research Service Center
    The National University Hospital of Iceland)

  • Rafn Benediktsson

    (University of Iceland
    The National University Hospital of Iceland)

  • Patrick Sulem

    (deCODE genetics/Amgen Inc.)

  • Ingileif Jonsdottir

    (deCODE genetics/Amgen Inc.
    University of Iceland
    Landspitali–The National University Hospital of Iceland)

  • Gisli Masson

    (deCODE genetics/Amgen Inc.)

  • Hilma Holm

    (deCODE genetics/Amgen Inc.)

  • Gudmundur L. Norddahl

    (deCODE genetics/Amgen Inc.)

  • Unnur Thorsteinsdottir

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Daniel F. Gudbjartsson

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Kari Stefansson

    (deCODE genetics/Amgen Inc.
    University of Iceland)

Abstract

Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10−42, β = −0.090) and confers risk of hip fracture (P = 1.0 × 10−8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.

Suggested Citation

  • Unnur Styrkarsdottir & Olafur A. Stefansson & Kristbjorg Gunnarsdottir & Gudmar Thorleifsson & Sigrun H. Lund & Lilja Stefansdottir & Kristinn Juliusson & Arna B. Agustsdottir & Florian Zink & Gisli H, 2019. "GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09860-0
    DOI: 10.1038/s41467-019-09860-0
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