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
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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