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

Styrkarsdottir, U; Stefansson, OA; Gunnarsdottir, K; Thorleifsson, G; Lund, SH; Stefansdottir, L; Juliusson, K; Agustsdottir, AB; Zink, F; Halldorsson, GH; Ivarsdottir, EV; Benonisdottir, S; Jonsson, H; Gylfason, A; Norland, K; Trajanoska, K; Boer, CG; Southam, L; Leung, JCS; Tang, NLS; Kwok, TCY; Lee, JSW; Ho, SC; Byrjalsen, I; Center, JR; Lee, SH; Koh, JM; Lohmander, LS; Ho-Pham, LT; Nguyen, TV; Eisman, JA; Woo, J; Leung, PC; Loughlin, J; Zeggini, E; Christiansen, C; Rivadeneira, F; van Meurs, J; Uitterlinden, AG; Mogensen, B; Ingvarsson, T; Sigurdsson, G; Benediktsson, R; Sulem, P; Jonsdottir, I; Masson, G; Holm, H; Norddahl, GL; Thorsteinsdottir, U; Gudbjartsson, DF; Stefansson, K

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

Styrkarsdottir, U Stefansson, OA Gunnarsdottir, K Thorleifsson, G Lund, SH Stefansdottir, L Juliusson, K Agustsdottir, AB Zink, F Halldorsson, GH Ivarsdottir, EV Benonisdottir, S Jonsson, H Gylfason, A Norland, K Trajanoska, K Boer, CG Southam, L Leung, JCS Tang, NLS Kwok, TCY Lee, JSW Ho, SC Byrjalsen, I Center, JR Lee, SH Koh, JM Lohmander, LS Ho-Pham, LT Nguyen, TV

Eisman, JA Woo, J Leung, PC Loughlin, J Zeggini, E Christiansen, C Rivadeneira, F van Meurs, J Uitterlinden, AG Mogensen, B Ingvarsson, T Sigurdsson, G Benediktsson, R Sulem, P Jonsdottir, I Masson, G Holm, H Norddahl, GL Thorsteinsdottir, U Gudbjartsson, DF Stefansson, K

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Publication Type:: Journal Article
Citation:: Nature Communications, 2019, 10 (1)
Issue Date:: 2019-12-01

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Field	Value	Language
dc.contributor.author	Styrkarsdottir, U	en_US
dc.contributor.author	Stefansson, OA	en_US
dc.contributor.author	Gunnarsdottir, K	en_US
dc.contributor.author	Thorleifsson, G	en_US
dc.contributor.author	Lund, SH	en_US
dc.contributor.author	Stefansdottir, L	en_US
dc.contributor.author	Juliusson, K	en_US
dc.contributor.author	Agustsdottir, AB	en_US
dc.contributor.author	Zink, F	en_US
dc.contributor.author	Halldorsson, GH	en_US
dc.contributor.author	Ivarsdottir, EV	en_US
dc.contributor.author	Benonisdottir, S	en_US
dc.contributor.author	Jonsson, H	en_US
dc.contributor.author	Gylfason, A	en_US
dc.contributor.author	Norland, K	en_US
dc.contributor.author	Trajanoska, K	en_US
dc.contributor.author	Boer, CG	en_US
dc.contributor.author	Southam, L	en_US
dc.contributor.author	Leung, JCS	en_US
dc.contributor.author	Tang, NLS	en_US
dc.contributor.author	Kwok, TCY	en_US
dc.contributor.author	Lee, JSW	en_US
dc.contributor.author	Ho, SC	en_US
dc.contributor.author	Byrjalsen, I	en_US
dc.contributor.author	Center, JR	en_US
dc.contributor.author	Lee, SH	en_US
dc.contributor.author	Koh, JM	en_US
dc.contributor.author	Lohmander, LS	en_US
dc.contributor.author	Ho-Pham, LT	en_US
dc.contributor.author	Nguyen, TV https://orcid.org/0000-0002-3246-6281	en_US
dc.contributor.author	Eisman, JA	en_US
dc.contributor.author	Woo, J	en_US
dc.contributor.author	Leung, PC	en_US
dc.contributor.author	Loughlin, J	en_US
dc.contributor.author	Zeggini, E	en_US
dc.contributor.author	Christiansen, C	en_US
dc.contributor.author	Rivadeneira, F	en_US
dc.contributor.author	van Meurs, J	en_US
dc.contributor.author	Uitterlinden, AG	en_US
dc.contributor.author	Mogensen, B	en_US
dc.contributor.author	Ingvarsson, T	en_US
dc.contributor.author	Sigurdsson, G	en_US
dc.contributor.author	Benediktsson, R	en_US
dc.contributor.author	Sulem, P	en_US
dc.contributor.author	Jonsdottir, I	en_US
dc.contributor.author	Masson, G	en_US
dc.contributor.author	Holm, H	en_US
dc.contributor.author	Norddahl, GL	en_US
dc.contributor.author	Thorsteinsdottir, U	en_US
dc.contributor.author	Gudbjartsson, DF	en_US
dc.contributor.author	Stefansson, K	en_US
dc.date.accessioned	2020-04-03T00:39:35Z
dc.date.available	2019-04-03	en_US
dc.date.available	2020-04-03T00:39:35Z
dc.date.issued	2019-12-01	en_US
dc.identifier.citation	Nature Communications, 2019, 10 (1)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/139754
dc.description.abstract	© 2019, The Author(s). 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.	en_US
dc.relation.ispartof	Nature Communications	en_US
dc.relation.isbasedon	10.1038/s41467-019-09860-0	en_US
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Bone and Bones	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Osteoarthritis	en_US
dc.subject.mesh	Hip Fractures	en_US
dc.subject.mesh	Genetic Predisposition to Disease	en_US
dc.subject.mesh	Collagen Type XI	en_US
dc.subject.mesh	MicroRNAs	en_US
dc.subject.mesh	Absorptiometry, Photon	en_US
dc.subject.mesh	Body Height	en_US
dc.subject.mesh	Risk Factors	en_US
dc.subject.mesh	Case-Control Studies	en_US
dc.subject.mesh	Follow-Up Studies	en_US
dc.subject.mesh	Bone Density	en_US
dc.subject.mesh	Alleles	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Aged	en_US
dc.subject.mesh	Aged, 80 and over	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Genome-Wide Association Study	en_US
dc.subject.mesh	Growth Differentiation Factor 5	en_US
dc.subject.mesh	Genetic Loci	en_US
dc.title	GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	10	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access	*
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	10	en_US

Abstract:

© 2019, The Author(s). 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/139754