Linkage of osteoporosis to chromosome 20p12 and association to BMP2

Unnur Styrkarsdottir, Jean-Baptiste Cazier, Augustine Kong, Ottar Rolfsson, Helene Larsen, Emma Bjarnadottir, Vala D Johannsdottir, Margret S Sigurdardottir, Yu Bagger, Claus Christiansen, Inga Reynisdottir, Struan F A Grant, Kristjan Jonasson, Michael L Frigge, Jeffrey R Gulcher, Gunnar Sigurdsson, Kari Stefansson

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207 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)E69
JournalPLoS Biology
Issue number3
Publication statusPublished - Dec 2003


  • Alleles
  • Bone Density
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Chromosome Mapping
  • Chromosomes, Human, Pair 20
  • Cohort Studies
  • Genetic Linkage
  • Genetic Variation
  • Genotype
  • Haplotypes
  • Humans
  • Iceland
  • Linkage Disequilibrium
  • Lod Score
  • Molecular Sequence Data
  • Mutation, Missense
  • Osteoporosis
  • Phenotype
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Transforming Growth Factor beta


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