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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Unnur Styrkarsdottir
  • Olafur A. Stefansson
  • Kristbjorg Gunnarsdottir
  • Gudmar Thorleifsson
  • Sigrun H. Lund
  • Lilja Stefansdottir
  • Kristinn Juliusson
  • Arna B. Agustsdottir
  • Florian Zink
  • Gisli H. Halldorsson
  • Erna V. Ivarsdottir
  • Stefania Benonisdottir
  • Hakon Jonsson
  • Arnaldur Gylfason
  • Kristjan Norland
  • Katerina Trajanoska
  • Cindy G. Boer
  • Lorraine Southam
  • Jason C.S. Leung
  • Nelson L.S. Tang
  • Timothy C.Y. Kwok
  • Jenny S.W. Lee
  • Suzanne C. Ho
  • Inger Byrjalsen
  • Jacqueline R. Center
  • Seung Hun Lee
  • Jung Min Koh
  • Lan T. Ho-Pham
  • Tuan V. Nguyen
  • John A. Eisman
  • Jean Woo
  • Ping C. Leung
  • John Loughlin
  • Eleftheria Zeggini
  • Claus Christiansen
  • Fernando Rivadeneira
  • Joyce van Meurs
  • Andre G. Uitterlinden
  • Brynjolfur Mogensen
  • Helgi Jonsson
  • Thorvaldur Ingvarsson
  • Gunnar Sigurdsson
  • Rafn Benediktsson
  • Patrick Sulem
  • Ingileif Jonsdottir
  • Gisli Masson
  • Hilma Holm
  • Gudmundur L. Norddahl
  • Unnur Thorsteinsdottir
  • Daniel F. Gudbjartsson
  • Kari Stefansson
Organisations
External organisations
  • University of Iceland
  • Erasmus University Medical Center
  • Wellcome Trust Sanger Institute
  • Wellcome Trust Centre for Human Genetics
  • Chinese University of Hong Kong
  • Prince of Wales Hospital Hong Kong
  • Alice Ho Miu Ling Nethersole Hospital
  • Nordic Bioscience AS
  • Garvan Institute of Medical Research
  • University of Notre Dame Australia
  • University of New South Wales
  • Ton Duc Thang University
  • University of Technology Sydney
  • University of Newcastle upon Tyne
  • Helmholtz Zentrum München
  • Akureyri Central Hospital
  • University of Akureyri
  • University of Ulsan
  • deCODE Genetics, Amgen, Inc.
  • University of Ulsan College of Medicine
  • National University Hospital of Iceland
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Orthopedics
Original languageEnglish
Article number2054
JournalNature Communications
Volume10
Issue number1
Publication statusPublished - 2019 May 3
Publication categoryResearch
Peer-reviewedYes