title: The genetics of bone mass and susceptibility to bone diseases.
abstract: Osteoporosis is characterized by low bone mass and an increased risk of fracture. Genetic factors, environmental factors and gene-environment interactions all contribute to a person's lifetime risk of developing an osteoporotic fracture. This Review summarizes key advances in understanding of the genetics of bone traits and their role in osteoporosis. Candidate-gene approaches dominated this field 20 years ago, but clinical and preclinical genetic studies published in the past 5 years generally utilize more-sophisticated and better-powered genome-wide association studies (GWAS). High-throughput DNA sequencing, large genomic databases and improved methods of data analysis have greatly accelerated the gene-discovery process. Linkage analyses of single-gene traits that segregate in families with extreme phenotypes have led to the elucidation of critical pathways controlling bone mass. For example, components of the Wnt-β-catenin signalling pathway have been validated (in both GWAS and functional studies) as contributing to various bone phenotypes. These notable advances in gene discovery suggest that the next decade will witness cataloguing of the hundreds of genes that influence bone mass and osteoporosis, which in turn will provide a roadmap for the development of new drugs that target diseases of low bone mass, including osteoporosis.
authors.affiliation: Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, Massachusetts 02131, USA.|Faculty of Medicine in the Galilee, Bar-Ilan University, 8 Henrietta Szold Street, Safed 13010, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Karasik
authors.affiliation: Departments of Internal Medicine and Epidemiology, Erasmus Medical Centre, Rotterdams-Gravendijkwal 230, 3015 CE, Netherlands.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.affiliation: Department of Oral and Craniofacial Sciences, University of Missouri-Kansas City School of Dentistry, 650 East 25th Street, Kansas City, Missouri 64108, USA.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Johnson
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics*; D001847:Bone Diseases / Q000235:genetics; D004195:Disease Models, Animal; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015576:Hyperostosis / Q000235:genetics; D010009:Osteochondrodysplasias / Q000235:genetics; D010013:Osteogenesis Imperfecta / Q000235:genetics; D010024:Osteoporosis / Q000235:genetics*; D010641:Phenotype; D017422:Sequence Analysis, DNA; D013576:Syndactyly / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics