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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ftpubmed:oai:pubmedcentral.nih.gov:270020 2023-05-15T16:50:57+02:00 Linkage of Osteoporosis to Chromosome 20p12 and Association to BMP2 Styrkarsdottir, Unnur Cazier, Jean-Baptiste Kong, Augustine Rolfsson, Ottar Larsen, Helene Bjarnadottir, Emma Johannsdottir, Vala D Sigurdardottir, Margret S Bagger, Yu Christiansen, Claus Reynisdottir, Inga Grant, Struan F. A Jonasson, Kristjan Frigge, Michael L Gulcher, Jeffrey R Sigurdsson, Gunnar Stefansson, Kari 2003-12 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC270020 http://www.ncbi.nlm.nih.gov/pubmed/14691541 https://doi.org/10.1371/journal.pbio.0000069 en eng Public Library of Science http://www.ncbi.nlm.nih.gov/pmc/articles/PMC270020 http://www.ncbi.nlm.nih.gov/pubmed/14691541 http://dx.doi.org/10.1371/journal.pbio.0000069 Copyright: © 2003 Styrkarsdottir et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited CC-BY Research Article Text 2003 ftpubmed https://doi.org/10.1371/journal.pbio.0000069 2013-08-29T17:18:59Z 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. Text Iceland PubMed Central (PMC) PLoS Biology 1 3 e69 |
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English |
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Research Article Styrkarsdottir, Unnur Cazier, Jean-Baptiste Kong, Augustine Rolfsson, Ottar Larsen, Helene Bjarnadottir, Emma Johannsdottir, Vala D Sigurdardottir, Margret S Bagger, Yu Christiansen, Claus Reynisdottir, Inga Grant, Struan F. A Jonasson, Kristjan Frigge, Michael L Gulcher, Jeffrey R Sigurdsson, Gunnar Stefansson, Kari Linkage of Osteoporosis to Chromosome 20p12 and Association to BMP2 |
topic_facet |
Research Article |
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 |
Text |
author |
Styrkarsdottir, Unnur Cazier, Jean-Baptiste Kong, Augustine Rolfsson, Ottar Larsen, Helene Bjarnadottir, Emma Johannsdottir, Vala D Sigurdardottir, Margret S Bagger, Yu Christiansen, Claus Reynisdottir, Inga Grant, Struan F. A Jonasson, Kristjan Frigge, Michael L Gulcher, Jeffrey R Sigurdsson, Gunnar Stefansson, Kari |
author_facet |
Styrkarsdottir, Unnur Cazier, Jean-Baptiste Kong, Augustine Rolfsson, Ottar Larsen, Helene Bjarnadottir, Emma Johannsdottir, Vala D Sigurdardottir, Margret S Bagger, Yu Christiansen, Claus Reynisdottir, Inga Grant, Struan F. A Jonasson, Kristjan Frigge, Michael L Gulcher, Jeffrey R Sigurdsson, Gunnar Stefansson, Kari |
author_sort |
Styrkarsdottir, Unnur |
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 |
2003 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC270020 http://www.ncbi.nlm.nih.gov/pubmed/14691541 https://doi.org/10.1371/journal.pbio.0000069 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC270020 http://www.ncbi.nlm.nih.gov/pubmed/14691541 http://dx.doi.org/10.1371/journal.pbio.0000069 |
op_rights |
Copyright: © 2003 Styrkarsdottir et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.1371/journal.pbio.0000069 |
container_title |
PLoS Biology |
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1 |
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3 |
container_start_page |
e69 |
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1766041056708657152 |