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An atlas of genetic determinants of forearm fracture

Nethander, Maria ; Movérare-Skrtic, Sofia ; Kämpe, Anders ; Coward, Eivind ; Reimann, Ene ; Grahnemo, Louise ; Borbély, Éva ; Helyes, Zsuzsanna ; Funck-Brentano, Thomas and Cohen-Solal, Martine , et al. (2023) In Nature Genetics 55(11). p.1820-1830
Abstract

Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are the most common clinically recognized osteoporotic fractures with a relatively high heritability. To establish an atlas of the genetic determinants of forearm fractures, we performed genome-wide association analyses including 100,026 forearm fracture cases. We identified 43 loci, including 26 new fracture loci. Although most fracture loci associated with bone mineral density, we also identified loci that primarily regulate bone quality parameters. Functional studies of one such locus, at TAC4, revealed that Tac4 –/– mice have reduced mechanical bone strength.... (More)

Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are the most common clinically recognized osteoporotic fractures with a relatively high heritability. To establish an atlas of the genetic determinants of forearm fractures, we performed genome-wide association analyses including 100,026 forearm fracture cases. We identified 43 loci, including 26 new fracture loci. Although most fracture loci associated with bone mineral density, we also identified loci that primarily regulate bone quality parameters. Functional studies of one such locus, at TAC4, revealed that Tac4 –/– mice have reduced mechanical bone strength. The strongest forearm fracture signal, at WNT16, displayed remarkable bone-site-specificity with no association with hip fractures. Tall stature and low body mass index were identified as new causal risk factors for fractures. The insights from this atlas may improve fracture prediction and enable therapeutic development to prevent fractures.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
55
issue
11
pages
11 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:37919453
  • scopus:85175830637
ISSN
1061-4036
DOI
10.1038/s41588-023-01527-3
language
English
LU publication?
yes
id
33a3d7c4-86fe-4926-adb8-a20e5a78fa40
date added to LUP
2023-11-23 11:43:34
date last changed
2024-04-20 15:11:04
@article{33a3d7c4-86fe-4926-adb8-a20e5a78fa40,
  abstract     = {{<p>Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are the most common clinically recognized osteoporotic fractures with a relatively high heritability. To establish an atlas of the genetic determinants of forearm fractures, we performed genome-wide association analyses including 100,026 forearm fracture cases. We identified 43 loci, including 26 new fracture loci. Although most fracture loci associated with bone mineral density, we also identified loci that primarily regulate bone quality parameters. Functional studies of one such locus, at TAC4, revealed that Tac4 <sup>–/–</sup> mice have reduced mechanical bone strength. The strongest forearm fracture signal, at WNT16, displayed remarkable bone-site-specificity with no association with hip fractures. Tall stature and low body mass index were identified as new causal risk factors for fractures. The insights from this atlas may improve fracture prediction and enable therapeutic development to prevent fractures.</p>}},
  author       = {{Nethander, Maria and Movérare-Skrtic, Sofia and Kämpe, Anders and Coward, Eivind and Reimann, Ene and Grahnemo, Louise and Borbély, Éva and Helyes, Zsuzsanna and Funck-Brentano, Thomas and Cohen-Solal, Martine and Tuukkanen, Juha and Koskela, Antti and Wu, Jianyao and Li, Lei and Lu, Tianyuan and Gabrielsen, Maiken E. and Mägi, Reedik and Hoff, Mari and Lerner, Ulf H. and Henning, Petra and Ullum, Henrik and Erikstrup, Christian and Brunak, Søren and Langhammer, Arnulf and Tuomi, Tiinamaija and Oddsson, Asmundur and Stefansson, Kari and Pettersson-Kymmer, Ulrika and Ostrowski, Sisse Rye and Pedersen, Ole Birger Vesterager and Styrkarsdottir, Unnur and Mäkitie, Outi and Hveem, Kristian and Richards, J. Brent and Ohlsson, Claes}},
  issn         = {{1061-4036}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1820--1830}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Genetics}},
  title        = {{An atlas of genetic determinants of forearm fracture}},
  url          = {{http://dx.doi.org/10.1038/s41588-023-01527-3}},
  doi          = {{10.1038/s41588-023-01527-3}},
  volume       = {{55}},
  year         = {{2023}},
}