Two Rare Mutations in the COL1A2 Gene Associate with Low Bone Mineral Density and Fractures in Iceland

Styrkarsdottir, U; Thorleifsson, G; Eiriksdottir, B; Gudjonsson, SA; Ingvarsson, T; Center, JR; Nguyen, TV; Eisman, JA; Christiansen, C; Thorsteinsdottir, U; Sigurdsson, G; Stefansson, K

Two Rare Mutations in the COL1A2 Gene Associate with Low Bone Mineral Density and Fractures in Iceland

Styrkarsdottir, U Thorleifsson, G Eiriksdottir, B Gudjonsson, SA Ingvarsson, T Center, JR Nguyen, TV

Eisman, JA Christiansen, C Thorsteinsdottir, U Sigurdsson, G Stefansson, K

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Publication Type:: Journal Article
Citation:: Journal of Bone and Mineral Research, 2016, 31 (1), pp. 173 - 179
Issue Date:: 2016-01-01

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Field	Value	Language
dc.contributor.author	Styrkarsdottir, U	en_US
dc.contributor.author	Thorleifsson, G	en_US
dc.contributor.author	Eiriksdottir, B	en_US
dc.contributor.author	Gudjonsson, SA	en_US
dc.contributor.author	Ingvarsson, T	en_US
dc.contributor.author	Center, JR	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	Christiansen, C	en_US
dc.contributor.author	Thorsteinsdottir, U	en_US
dc.contributor.author	Sigurdsson, G	en_US
dc.contributor.author	Stefansson, K	en_US
dc.date.available	2015-07-27	en_US
dc.date.issued	2016-01-01	en_US
dc.identifier.citation	Journal of Bone and Mineral Research, 2016, 31 (1), pp. 173 - 179	en_US
dc.identifier.issn	0884-0431	en_US
dc.identifier.uri	http://hdl.handle.net/10453/122611
dc.description.abstract	© 2015 American Society for Bone and Mineral Research. We conducted a genome-wide association study of low bone mineral density (BMD) at the hip and spine utilizing sequence variants found through whole-genome sequencing of 2636 Icelanders. We found two rare missense mutations, p.Gly496Ala and p.Gly703Ser, in the COL1A2 gene that associate with measures of osteoporosis in Icelanders. Mutations in COL1A2 are known to cause the autosomal dominant disorder osteogenesis imperfecta. Both variants associate with low BMD and with osteoporotic fractures. p.Gly496Ala (frequency of 0.105%) shows the strongest association with low BMD at the spine (p = 1.8 × 10-7, odds ratio [OR] = 4.61 [95% confidence interval (CI) 2.59, 8.18]), whereas p.Gly703Ser (frequency of 0.050%) is most strongly associated with low BMD at the hip (p = 1.9 × 10-8, OR = 9.34 [95% CI 4.28, 20.3]). Association with fractures was p = 2.2 × 10-5, OR = 3.75 (95% CI 2.03, 6.93) and p = 0.0023, OR = 4.32 (95% CI 1.69, 11.1), respectively. The carriers of these variants do not have signs of osteogenesis imperfecta other than low BMD, demonstrating that similar mutations in COL1A2 can affect skeletal phenotypes in more than one way.	en_US
dc.relation.ispartof	Journal of Bone and Mineral Research	en_US
dc.relation.isbasedon	10.1002/jbmr.2604	en_US
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.classification	Anatomy & Morphology	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Collagen Type I	en_US
dc.subject.mesh	Bone Density	en_US
dc.subject.mesh	Polymorphism, Single Nucleotide	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	Fractures, Bone	en_US
dc.subject.mesh	INDEL Mutation	en_US
dc.title	Two Rare Mutations in the COL1A2 Gene Associate with Low Bone Mineral Density and Fractures in Iceland	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	31	en_US
utslib.for	0903 Biomedical Engineering	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	09 Engineering	en_US
utslib.for	11 Medical and Health Sciences	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	closed_access	*
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	31	en_US

Abstract:

© 2015 American Society for Bone and Mineral Research. We conducted a genome-wide association study of low bone mineral density (BMD) at the hip and spine utilizing sequence variants found through whole-genome sequencing of 2636 Icelanders. We found two rare missense mutations, p.Gly496Ala and p.Gly703Ser, in the COL1A2 gene that associate with measures of osteoporosis in Icelanders. Mutations in COL1A2 are known to cause the autosomal dominant disorder osteogenesis imperfecta. Both variants associate with low BMD and with osteoporotic fractures. p.Gly496Ala (frequency of 0.105%) shows the strongest association with low BMD at the spine (p = 1.8 × 10-7, odds ratio [OR] = 4.61 [95% confidence interval (CI) 2.59, 8.18]), whereas p.Gly703Ser (frequency of 0.050%) is most strongly associated with low BMD at the hip (p = 1.9 × 10-8, OR = 9.34 [95% CI 4.28, 20.3]). Association with fractures was p = 2.2 × 10-5, OR = 3.75 (95% CI 2.03, 6.93) and p = 0.0023, OR = 4.32 (95% CI 1.69, 11.1), respectively. The carriers of these variants do not have signs of osteogenesis imperfecta other than low BMD, demonstrating that similar mutations in COL1A2 can affect skeletal phenotypes in more than one way.

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

http://hdl.handle.net/10453/122611