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      Using GWAS to identify novel therapeutic targets for osteoporosis

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          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.

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          Author and article information

          Journal
          101280339
          33033
          Transl Res
          Transl Res
          Translational research : the journal of laboratory and clinical medicine
          1931-5244
          1878-1810
          13 January 2017
          27 October 2016
          March 2017
          01 March 2018
          : 181
          : 15-26
          Affiliations
          [1 ]Center for Public Health Genomics and Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA 22908
          [2 ]Center for Public Health Genomics and Departments of Public Health Science and Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA 22908
          Author notes
          Corresponding author: Dr. Charles R. Farber, Center for Public Health Genomics at UVA, PO Box 800717 Charlottesville, VA 22908. crf2s@ 123456virginia.edu . (434) 243-8584
          Article
          PMC5357198 PMC5357198 5357198 nihpa842326
          10.1016/j.trsl.2016.10.009
          5357198
          27837649
          07caab41-8ef9-4fea-a967-59da76673673
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