Linkage of Osteoporosis to Chromosome 20p12 and Association to BMP2

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Linkage of Osteoporosis to Chromosome 20p12 and Association to BMP2

Public Library of Science
Publication Date
Nov 03, 2003
  • Biology


plbi-01-03-08 351..360 Linkage of Osteoporosis to Chromosome 20p12 and Association to BMP2 Unnur Styrkarsdottir 1*, Jean-Baptiste Cazier 1 , Augustine Kong 1 , Ottar Rolfsson 1 , Helene Larsen 1 , Emma Bjarnadottir 1 , Vala D. Johannsdottir 1 , Margret S. Sigurdardottir 1 , Yu Bagger 2 , Claus Christiansen 2 , Inga Reynisdottir 1 , Struan F. A. Grant 1 , Kristjan Jonasson 1 , Michael L. Frigge 1 , Jeffrey R. Gulcher 1[, Gunnar Sigurdsson 3*, Kari Stefansson 1[* 1 deCODE Genetics, Reykjavik, Iceland, 2 Center for Clinical and Basic Research A/S, Ballerup, Denmark, 3 National University Hospital, Reykjavik, Iceland 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 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 ost


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