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

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


Title: GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures
Author: Styrkarsdottir, Unnur   orcid.org/0000-0001-8146-8278
Stefansson, Olafur A.
Gunnarsdottir, Kristbjorg
Thorleifsson, Gudmar   orcid.org/0000-0003-4623-9087
Lund, Sigrun H.
Stefansdottir, Lilja
Juliusson, Kristinn
Agustsdottir, Arna B.
Zink, Florian
Halldorsson, Gisli H.
... 42 more authors Show all authors
Date: 2019-05-03
Language: English
Scope: 2054
University/Institute: Háskólinn á Akureyri
University of Akureyri
Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HA)
School of Health Sciences (UA)
Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Heilbrigðisvísindastofnun (HA)
Research Centre for Health Science (UA)
Læknadeild (HÍ)
Faculty of Medicine (UI)
Series: Nature Communications;10(1)
ISSN: 2041-1723
DOI: 10.1038/s41467-019-09860-0
Subject: Genetics; Fractures; Osteoarthritis; Erfðafræði; Beinbrot; Slitgigt
URI: https://hdl.handle.net/20.500.11815/1171

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Citation:

Styrkarsdottir, U., Stefansson, O. A., Gunnarsdottir, K., Thorleifsson, G., Lund, S. H., Stefansdottir, L., . . . Stefansson, K. (2019). GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures. Nature Communications, 10(1), 2054. doi:10.1038/s41467-019-09860-0

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.

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