Linkage of osteoporosis to chromosome 20p12 and association to BMP2
Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis famil...
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ftuloxford:oai:ora.ox.ac.uk:uuid:1db4dedd-4105-461d-a8bf-1a641c1abee9 2024-10-06T13:50:03+00:00 Linkage of osteoporosis to chromosome 20p12 and association to BMP2 Styrkarsdottir, U Cazier, J Kong, A Rolfsson, O Larsen, H Bjarnadottir, E Johannsdottir, V Sigurdardottir, MS Bagger, Y Christiansen, C Reynisdottir, I Grant, S Jonasson, K Frigge, M Gulcher, JR Sigurdsson, G Stefansson, K 2016-07-28 https://doi.org/10.1371/journal.pbio.0000069 https://ora.ox.ac.uk/objects/uuid:1db4dedd-4105-461d-a8bf-1a641c1abee9 eng eng Public Library of Science doi:10.1371/journal.pbio.0000069 https://ora.ox.ac.uk/objects/uuid:1db4dedd-4105-461d-a8bf-1a641c1abee9 https://doi.org/10.1371/journal.pbio.0000069 info:eu-repo/semantics/openAccess CC Attribution (CC BY) Journal article 2016 ftuloxford https://doi.org/10.1371/journal.pbio.0000069 2024-09-06T07:47:29Z Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis families in Iceland, using a phenotype that combines osteoporotic fractures and BMD measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing LOD, 5.10; p value, 6.3 × 10−7), results that are statistically significant after adjusting for the number of phenotypes tested and the genome-wide search. A follow-up association analysis using closely spaced polymorphic markers was performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients. The association is seen with many definitions of an osteoporotic phenotype, including osteoporotic fractures as well as low BMD, both before and after menopause. A replication study with a Danish cohort of postmenopausal women was conducted to confirm the contribution of the three identified variants. In conclusion, we find that a region on the short arm of Chromosome 20 contains a gene or genes that appear to be a major risk factor for osteoporosis and osteoporotic fractures, and our evidence supports the view that BMP2 is at least one of these genes. Article in Journal/Newspaper Iceland ORA - Oxford University Research Archive PLoS Biology 1 3 e69 |
institution |
Open Polar |
collection |
ORA - Oxford University Research Archive |
op_collection_id |
ftuloxford |
language |
English |
description |
Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis families in Iceland, using a phenotype that combines osteoporotic fractures and BMD measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing LOD, 5.10; p value, 6.3 × 10−7), results that are statistically significant after adjusting for the number of phenotypes tested and the genome-wide search. A follow-up association analysis using closely spaced polymorphic markers was performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients. The association is seen with many definitions of an osteoporotic phenotype, including osteoporotic fractures as well as low BMD, both before and after menopause. A replication study with a Danish cohort of postmenopausal women was conducted to confirm the contribution of the three identified variants. In conclusion, we find that a region on the short arm of Chromosome 20 contains a gene or genes that appear to be a major risk factor for osteoporosis and osteoporotic fractures, and our evidence supports the view that BMP2 is at least one of these genes. |
format |
Article in Journal/Newspaper |
author |
Styrkarsdottir, U Cazier, J Kong, A Rolfsson, O Larsen, H Bjarnadottir, E Johannsdottir, V Sigurdardottir, MS Bagger, Y Christiansen, C Reynisdottir, I Grant, S Jonasson, K Frigge, M Gulcher, JR Sigurdsson, G Stefansson, K |
spellingShingle |
Styrkarsdottir, U Cazier, J Kong, A Rolfsson, O Larsen, H Bjarnadottir, E Johannsdottir, V Sigurdardottir, MS Bagger, Y Christiansen, C Reynisdottir, I Grant, S Jonasson, K Frigge, M Gulcher, JR Sigurdsson, G Stefansson, K Linkage of osteoporosis to chromosome 20p12 and association to BMP2 |
author_facet |
Styrkarsdottir, U Cazier, J Kong, A Rolfsson, O Larsen, H Bjarnadottir, E Johannsdottir, V Sigurdardottir, MS Bagger, Y Christiansen, C Reynisdottir, I Grant, S Jonasson, K Frigge, M Gulcher, JR Sigurdsson, G Stefansson, K |
author_sort |
Styrkarsdottir, U |
title |
Linkage of osteoporosis to chromosome 20p12 and association to BMP2 |
title_short |
Linkage of osteoporosis to chromosome 20p12 and association to BMP2 |
title_full |
Linkage of osteoporosis to chromosome 20p12 and association to BMP2 |
title_fullStr |
Linkage of osteoporosis to chromosome 20p12 and association to BMP2 |
title_full_unstemmed |
Linkage of osteoporosis to chromosome 20p12 and association to BMP2 |
title_sort |
linkage of osteoporosis to chromosome 20p12 and association to bmp2 |
publisher |
Public Library of Science |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pbio.0000069 https://ora.ox.ac.uk/objects/uuid:1db4dedd-4105-461d-a8bf-1a641c1abee9 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
doi:10.1371/journal.pbio.0000069 https://ora.ox.ac.uk/objects/uuid:1db4dedd-4105-461d-a8bf-1a641c1abee9 https://doi.org/10.1371/journal.pbio.0000069 |
op_rights |
info:eu-repo/semantics/openAccess CC Attribution (CC BY) |
op_doi |
https://doi.org/10.1371/journal.pbio.0000069 |
container_title |
PLoS Biology |
container_volume |
1 |
container_issue |
3 |
container_start_page |
e69 |
_version_ |
1812178128754180096 |