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Cited by 248Bone health and osteoporosis researchGenetic Associations and EpidemiologyBone Metabolism and Diseases

Linkage of Osteoporosis to Chromosome 20p12 and Association to BMP2

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Styrkarsdottir, Unnur, Cazier, Jean-Baptiste, Kong, Augustine, Rolfsson, Ottar, Larsen, Helene, Bjarnadottir, Emma, Johannsdottir, Vala D, Sigurdardottir, Margret S +9 more·2003·PLoS Biology
DOI 10.1371/journal.pbio.0000069PMC PMC270020
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Abstract

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 x 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.

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  • The largest study, in Icelandic and Danish cohorts, links BMP2 polymorphisms to low BMD and fracture risk.

    “the largest study to date, in Icelandic and Danish cohorts, suggests that polymorphisms of the BMP2 gene are linked to low BMD and fracture risk”

    From Pathogenesis of osteoporosis: concepts, conflicts, and prospects (2005) · cites this paper as [79]

    The Abstract and Results (Haplotype Confirmation in Danish Cohort; page numbers unavailable) report BMP2-variant associations with low BMD and osteoporotic fractures in Icelandic patients, with supporting results in a Danish cohort. The copy describes a large Icelandic study but does not establish that it was the largest study to date. (LLM, conf=0.82)

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Authors
Styrkarsdottir, U., Cazier, J.-B., Kong, A., Rolfsson, O., Larsen, H., Bjarnadottir, E., Johannsdottir, V. D., Sigurdardottir, M. S., Bagger, Y., Christiansen, C., Reynisdottir, I., Grant, S. F. A., Jonasson, K., Frigge, M. L., Gulcher, J. R., Sigurdsson, G., & Stefansson, K.
Affiliations
  • deCODE Genetics (Iceland) (IS)
  • Center for Clinical & Basic Research (DK)
  • National University Hospital of Iceland (IS)
Corresponding author
Sigurdsson, Gunnar
ORCID
Venue
PLoS Biology
Publisher
Public Library of Science (PLoS)
Published
2003-11-03
Volume
1
Issue
3
Pages
e69
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
DOI
10.1371/journal.pbio.0000069
PMC
PMC270020
OpenAlex
W2085266575
Cited by
248
References
1
Citations by year
2024: 2 · 2023: 2 · 2022: 2 · 2021: 9 · 2019: 7 · 2018: 6 · 2017: 9 · 2016: 7 · 2015: 8 · 2014: 8 · 2013: 12 · 2012: 12
FWCI
22.84
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
  • Hirsla (Landspítali University Hospital) (submittedVersion)
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords
osteoporosis, osteoporotic fractures, BMP-2, genetic linkage, genetic association, osteopenia, postmenopausal women, Icelandic families, single nucleotide polymorphisms, missense polymorphisms
MeSH terms
Alleles, Chromosome Mapping, Chromosomes, Human, Pair 20, Genotype, Haplotypes, Humans, Iceland, Genetic Linkage, Lod Score, Molecular Sequence Data, Osteoporosis, Phenotype, Polymorphism, Genetic, Risk Factors, Genetic Variation, Cohort Studies, Bone Density, Linkage Disequilibrium, Transforming Growth Factor beta, Bone Morphogenetic Proteins, Mutation, Missense, Polymorphism, Single Nucleotide, Bone Morphogenetic Protein 2

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