Two Rare Mutations in the COL1A2 Gene Associate with Low Bone Mineral Density and Fractures in Iceland
© 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.Gly...
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ftunivtsydney:oai:opus.lib.uts.edu.au:10453/122611 2023-05-15T16:48:00+02:00 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 2016-01-01 application/pdf http://hdl.handle.net/10453/122611 unknown Journal of Bone and Mineral Research 10.1002/jbmr.2604 Journal of Bone and Mineral Research, 2016, 31 (1), pp. 173 - 179 0884-0431 http://hdl.handle.net/10453/122611 info:eu-repo/semantics/closedAccess Anatomy & Morphology Humans Collagen Type I Bone Density Polymorphism Single Nucleotide Aged 80 and over Middle Aged Iceland Female Male Fractures Bone INDEL Mutation Journal Article 2016 ftunivtsydney 2022-03-13T13:29:15Z © 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. Article in Journal/Newspaper Iceland University of Technology Sydney: OPUS - Open Publications of UTS Scholars Indel’ ENVELOPE(35.282,35.282,66.963,66.963) |
institution |
Open Polar |
collection |
University of Technology Sydney: OPUS - Open Publications of UTS Scholars |
op_collection_id |
ftunivtsydney |
language |
unknown |
topic |
Anatomy & Morphology Humans Collagen Type I Bone Density Polymorphism Single Nucleotide Aged 80 and over Middle Aged Iceland Female Male Fractures Bone INDEL Mutation |
spellingShingle |
Anatomy & Morphology Humans Collagen Type I Bone Density Polymorphism Single Nucleotide Aged 80 and over Middle Aged Iceland Female Male Fractures Bone INDEL Mutation 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 |
topic_facet |
Anatomy & Morphology Humans Collagen Type I Bone Density Polymorphism Single Nucleotide Aged 80 and over Middle Aged Iceland Female Male Fractures Bone INDEL Mutation |
description |
© 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. |
format |
Article in Journal/Newspaper |
author |
Styrkarsdottir, U Thorleifsson, G Eiriksdottir, B Gudjonsson, SA Ingvarsson, T Center, JR Nguyen, TV Eisman, JA Christiansen, C Thorsteinsdottir, U Sigurdsson, G Stefansson, K |
author_facet |
Styrkarsdottir, U Thorleifsson, G Eiriksdottir, B Gudjonsson, SA Ingvarsson, T Center, JR Nguyen, TV Eisman, JA Christiansen, C Thorsteinsdottir, U Sigurdsson, G Stefansson, K |
author_sort |
Styrkarsdottir, U |
title |
Two Rare Mutations in the COL1A2 Gene Associate with Low Bone Mineral Density and Fractures in Iceland |
title_short |
Two Rare Mutations in the COL1A2 Gene Associate with Low Bone Mineral Density and Fractures in Iceland |
title_full |
Two Rare Mutations in the COL1A2 Gene Associate with Low Bone Mineral Density and Fractures in Iceland |
title_fullStr |
Two Rare Mutations in the COL1A2 Gene Associate with Low Bone Mineral Density and Fractures in Iceland |
title_full_unstemmed |
Two Rare Mutations in the COL1A2 Gene Associate with Low Bone Mineral Density and Fractures in Iceland |
title_sort |
two rare mutations in the col1a2 gene associate with low bone mineral density and fractures in iceland |
publishDate |
2016 |
url |
http://hdl.handle.net/10453/122611 |
long_lat |
ENVELOPE(35.282,35.282,66.963,66.963) |
geographic |
Indel’ |
geographic_facet |
Indel’ |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
Journal of Bone and Mineral Research 10.1002/jbmr.2604 Journal of Bone and Mineral Research, 2016, 31 (1), pp. 173 - 179 0884-0431 http://hdl.handle.net/10453/122611 |
op_rights |
info:eu-repo/semantics/closedAccess |
_version_ |
1766038099160203264 |