title: Using GWAS to identify novel therapeutic targets for osteoporosis.
abstract: Osteoporosis is a common, increasingly prevalent, global health burden characterized by low bone mineral density (BMD) and increased risk of fracture. Despite its significant impact on human health, there is currently a lack of highly effective treatments free of side effects for osteoporosis. Therefore, a major goal in the field is to identify new drug targets. Genetic discovery has been shown to be effective in the unbiased identification of novel drug targets and genome-wide association studies (GWASs) have begun to provide insight into genetic basis of osteoporosis. Over the last decade, GWASs have led to the identification of ∼100 loci associated with BMD and other bone traits related to risk of fracture. However, there have been limited efforts to identify the causal genes underlying the GWAS loci or the mechanisms by which GWAS loci alter bone physiology. In this review, we summarize the current state of the field and discuss strategies for causal gene discovery and the evidence that the novel genes underlying GWAS loci are likely to be a new source of drug targets.
authors.affiliation: Center for Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, Va; Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, Va.
authors.forename: Olivia L
authors.initials: OL
authors.lastname: Sabik
authors.affiliation: Center for Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, Va; Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, Va; Department of Public Health Science, School of Medicine, University of Virginia, Charlottesville, Va. Electronic address: crf2s@virginia.edu.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Farber
mesh_terms: D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study; D023281:Genomics; D006801:Humans; D058990:Molecular Targeted Therapy; D010024:Osteoporosis / Q000235:genetics* / Q000628:therapy*; D019655:Quantitative Trait, Heritable