Chromosome Locus and Candidate Gene for Osteoporosis Identified
Autor: | Helene Larsen, Jean-Baptiste Cazier, Michael L. Frigge, Jeffrey R. Gulcher, Emma Bjarnadottir, Yu Z. Bagger, Augustine Kong, Unnur Styrkarsdottir, Margret S Sigurdardottir, Struan F.A. Grant, Kristján Jónasson, Kari Stefansson, Inga Reynisdottir, Ottar Rolfsson, Gunnar Sigurdsson, Vala Drofn Johannsdottir, Claus Christiansen |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
Linkage disequilibrium
Bone density Genotype QH301-705.5 Genetic Linkage Osteoporosis Molecular Sequence Data Chromosomes Human Pair 20 Iceland Mutation Missense Bone Morphogenetic Protein 2 Single-nucleotide polymorphism Biology Bioinformatics Genetics/Genomics/Gene Therapy Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology Linkage Disequilibrium Cohort Studies Genetic linkage Bone Density Risk Factors Transforming Growth Factor beta Homo (Human) medicine Humans Biology (General) Alleles Genetic association Polymorphism Genetic General Immunology and Microbiology General Neuroscience Haplotype Chromosome Mapping Genetic Variation Bone fracture medicine.disease Phenotype Haplotypes Bone Morphogenetic Proteins Lod Score General Agricultural and Biological Sciences Research Article |
Zdroj: | PLoS Biology PLoS Biology, Vol 1, Iss 3, p E69 (2003) |
Popis: | 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. Genetic analysis of Icelandic families and a replication study in a Danish population provide evidence that variation in the gene BMP2 might contribute to osteoporosis |
Databáze: | OpenAIRE |
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