Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures

Styrkarsdottir, U; Thorleifsson, G; Gudjonsson, SA; Sigurdsson, A; Center, JR; Lee, SH; Nguyen, TV; Kwok, TCY; Lee, JSW; Ho, SC; Woo, J; Leung, PC; Kim, BJ; Rafnar, T; Kiemeney, LA; Ingvarsson, T; Koh, JM; Tang, NLS; Eisman, JA; Christiansen, C; Sigurdsson, G; Thorsteinsdottir, U; Stefansson, K

Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures

Styrkarsdottir, U Thorleifsson, G Gudjonsson, SA Sigurdsson, A Center, JR Lee, SH Nguyen, TV

Kwok, TCY Lee, JSW Ho, SC Woo, J Leung, PC Kim, BJ Rafnar, T Kiemeney, LA Ingvarsson, T Koh, JM Tang, NLS Eisman, JA Christiansen, C Sigurdsson, G Thorsteinsdottir, U Stefansson, K

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Publication Type:: Journal Article
Citation:: Nature Communications, 2016, 7
Issue Date:: 2016-01-06

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Field	Value	Language
dc.contributor.author	Styrkarsdottir, U	en_US
dc.contributor.author	Thorleifsson, G	en_US
dc.contributor.author	Gudjonsson, SA	en_US
dc.contributor.author	Sigurdsson, A	en_US
dc.contributor.author	Center, JR	en_US
dc.contributor.author	Lee, SH	en_US
dc.contributor.author	Nguyen, TV https://orcid.org/0000-0002-3246-6281	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	Woo, J	en_US
dc.contributor.author	Leung, PC	en_US
dc.contributor.author	Kim, BJ	en_US
dc.contributor.author	Rafnar, T	en_US
dc.contributor.author	Kiemeney, LA	en_US
dc.contributor.author	Ingvarsson, T	en_US
dc.contributor.author	Koh, JM	en_US
dc.contributor.author	Tang, NLS	en_US
dc.contributor.author	Eisman, JA	en_US
dc.contributor.author	Christiansen, C	en_US
dc.contributor.author	Sigurdsson, G	en_US
dc.contributor.author	Thorsteinsdottir, U	en_US
dc.contributor.author	Stefansson, K	en_US
dc.date.available	2015-11-06	en_US
dc.date.issued	2016-01-06	en_US
dc.identifier.citation	Nature Communications, 2016, 7	en_US
dc.identifier.uri	http://hdl.handle.net/10453/117270
dc.description.abstract	Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, represented by rs28377268 (freq. 11.4-22.6%) that associates with reduced spine BMD (P=1.0 × 10-11, b=-0.09). We also identified a new spine BMD signal in RSPO3, rs577721086 (freq. 6.8%), that associates with increased spine BMD (P=6.6×10-10, b=0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the PTCH1 and RSPO3 genes that is in line with their influence on BMD and known biological function of these genes. Additional new BMD signals were also found at the AXIN1 and SOST loci and a new lead SNP at the EN1 locus. DOI: 10.1038/ncomms10129 OPEN 1.	en_US
dc.relation.ispartof	Nature Communications	en_US
dc.relation.isbasedon	10.1038/ncomms10129	en_US
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Spine	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Osteoporosis	en_US
dc.subject.mesh	Fractures, Spontaneous	en_US
dc.subject.mesh	Thrombospondins	en_US
dc.subject.mesh	Receptors, Cell Surface	en_US
dc.subject.mesh	Gene Expression Regulation	en_US
dc.subject.mesh	Bone Density	en_US
dc.subject.mesh	Genotype	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	Iceland	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Genetic Variation	en_US
dc.subject.mesh	Genome-Wide Association Study	en_US
dc.subject.mesh	Patched Receptors	en_US
dc.subject.mesh	Patched-1 Receptor	en_US
dc.title	Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures	en_US
dc.type	Journal Article
utslib.citation.volume	7	en_US
utslib.for	0903 Biomedical Engineering	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.publication-status	Published	en_US
pubs.volume	7	en_US

Abstract:

Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, represented by rs28377268 (freq. 11.4-22.6%) that associates with reduced spine BMD (P=1.0 × 10-11, b=-0.09). We also identified a new spine BMD signal in RSPO3, rs577721086 (freq. 6.8%), that associates with increased spine BMD (P=6.6×10-10, b=0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the PTCH1 and RSPO3 genes that is in line with their influence on BMD and known biological function of these genes. Additional new BMD signals were also found at the AXIN1 and SOST loci and a new lead SNP at the EN1 locus. DOI: 10.1038/ncomms10129 OPEN 1.

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http://hdl.handle.net/10453/117270