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

Styrkarsdottir, Unnur; Stefansson, Olafur A.; Gunnarsdottir, Kristbjorg; Thorleifsson, Gudmar; Lund, Sigrun H.; Stefansdottir, Lilja; Juliusson, Kristinn; Agustsdottir, Arna B.; Zink, Florian and Halldorsson, Gisli H., et al. (2019) In Nature Communications 10(1).
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
... (More)


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.

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Nature Communications
volume
10
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1
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Nature Publishing Group
external identifiers
  • scopus:85065194502
ISSN
2041-1723
DOI
10.1038/s41467-019-09860-0
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English
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1dcd3cc7-b010-4fc7-b450-49acaa552500
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@article{1dcd3cc7-b010-4fc7-b450-49acaa552500,
  abstract     = {<p><br>
                                                         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                             <br>
                            <sup>−42</sup><br>
                                                         , β = −0.090) and confers risk of hip fracture (P = 1.0 × 10                             <br>
                            <sup>−8</sup><br>
                                                         , 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.                         <br>
                        </p>},
  articleno    = {2054},
  author       = {Styrkarsdottir, Unnur and Stefansson, Olafur A. and Gunnarsdottir, Kristbjorg and Thorleifsson, Gudmar and Lund, Sigrun H. and Stefansdottir, Lilja and Juliusson, Kristinn and Agustsdottir, Arna B. and Zink, Florian and Halldorsson, Gisli H. and Ivarsdottir, Erna V. and Benonisdottir, Stefania and Jonsson, Hakon and Gylfason, Arnaldur and Norland, Kristjan and Trajanoska, Katerina and Boer, Cindy G. and Southam, Lorraine and Leung, Jason C.S. and Tang, Nelson L.S. and Kwok, Timothy C.Y. and Lee, Jenny S.W. and Ho, Suzanne C. and Byrjalsen, Inger and Center, Jacqueline R. and Lee, Seung Hun and Koh, Jung Min and Lohmander, L. Stefan and Ho-Pham, Lan T. and Nguyen, Tuan V. and Eisman, John A. and Woo, Jean and Leung, Ping C. and Loughlin, John and Zeggini, Eleftheria and Christiansen, Claus and Rivadeneira, Fernando and van Meurs, Joyce and Uitterlinden, Andre G. and Mogensen, Brynjolfur and Jonsson, Helgi and Ingvarsson, Thorvaldur and Sigurdsson, Gunnar and Benediktsson, Rafn and Sulem, Patrick and Jonsdottir, Ingileif and Masson, Gisli and Holm, Hilma and Norddahl, Gudmundur L. and Thorsteinsdottir, Unnur and Gudbjartsson, Daniel F. and Stefansson, Kari},
  issn         = {2041-1723},
  language     = {eng},
  month        = {05},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures},
  url          = {http://dx.doi.org/10.1038/s41467-019-09860-0},
  volume       = {10},
  year         = {2019},
}