Two Rare Mutations in the COL1A2 Gene Associate With Low Bone Mineral Density and Fractures in Iceland
ABSTRACT 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...
Published in: | Journal of Bone and Mineral Research |
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crwiley:10.1002/jbmr.2604 2023-12-03T10:24:54+01:00 Two Rare Mutations in the COL1A2 Gene Associate With Low Bone Mineral Density and Fractures in Iceland Styrkarsdottir, Unnur Thorleifsson, Gudmar Eiriksdottir, Berglind Gudjonsson, Sigurjon A Ingvarsson, Thorvaldur Center, Jacqueline R Nguyen, Tuan V Eisman, John A Christiansen, Claus Thorsteinsdottir, Unnur Sigurdsson, Gunnar Stefansson, Kari Icelandic deCODE study, the Danish PERF study 2015 http://dx.doi.org/10.1002/jbmr.2604 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjbmr.2604 https://onlinelibrary.wiley.com/doi/full/10.1002/jbmr.2604 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Journal of Bone and Mineral Research volume 31, issue 1, page 173-179 ISSN 0884-0431 1523-4681 Orthopedics and Sports Medicine Endocrinology, Diabetes and Metabolism journal-article 2015 crwiley https://doi.org/10.1002/jbmr.2604 2023-11-09T14:14:23Z ABSTRACT 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. © 2015 American Society for Bone and Mineral Research. Article in Journal/Newspaper Iceland Wiley Online Library (via Crossref) Journal of Bone and Mineral Research 31 1 173 179 |
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Open Polar |
collection |
Wiley Online Library (via Crossref) |
op_collection_id |
crwiley |
language |
English |
topic |
Orthopedics and Sports Medicine Endocrinology, Diabetes and Metabolism |
spellingShingle |
Orthopedics and Sports Medicine Endocrinology, Diabetes and Metabolism Styrkarsdottir, Unnur Thorleifsson, Gudmar Eiriksdottir, Berglind Gudjonsson, Sigurjon A Ingvarsson, Thorvaldur Center, Jacqueline R Nguyen, Tuan V Eisman, John A Christiansen, Claus Thorsteinsdottir, Unnur Sigurdsson, Gunnar Stefansson, Kari Two Rare Mutations in the COL1A2 Gene Associate With Low Bone Mineral Density and Fractures in Iceland |
topic_facet |
Orthopedics and Sports Medicine Endocrinology, Diabetes and Metabolism |
description |
ABSTRACT 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. © 2015 American Society for Bone and Mineral Research. |
author2 |
Icelandic deCODE study, the Danish PERF study |
format |
Article in Journal/Newspaper |
author |
Styrkarsdottir, Unnur Thorleifsson, Gudmar Eiriksdottir, Berglind Gudjonsson, Sigurjon A Ingvarsson, Thorvaldur Center, Jacqueline R Nguyen, Tuan V Eisman, John A Christiansen, Claus Thorsteinsdottir, Unnur Sigurdsson, Gunnar Stefansson, Kari |
author_facet |
Styrkarsdottir, Unnur Thorleifsson, Gudmar Eiriksdottir, Berglind Gudjonsson, Sigurjon A Ingvarsson, Thorvaldur Center, Jacqueline R Nguyen, Tuan V Eisman, John A Christiansen, Claus Thorsteinsdottir, Unnur Sigurdsson, Gunnar Stefansson, Kari |
author_sort |
Styrkarsdottir, Unnur |
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 |
publisher |
Wiley |
publishDate |
2015 |
url |
http://dx.doi.org/10.1002/jbmr.2604 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjbmr.2604 https://onlinelibrary.wiley.com/doi/full/10.1002/jbmr.2604 |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Journal of Bone and Mineral Research volume 31, issue 1, page 173-179 ISSN 0884-0431 1523-4681 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/jbmr.2604 |
container_title |
Journal of Bone and Mineral Research |
container_volume |
31 |
container_issue |
1 |
container_start_page |
173 |
op_container_end_page |
179 |
_version_ |
1784273498503380992 |