Using GWAS to identify novel therapeutic targets for osteoporosis
Olivia L Sabik1, Charles R Farber2
1Center 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.
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.
Insights
Osteoporosis treatments lack efficacy and safety. Genome-wide association studies (GWASs) identify genetic targets for osteoporosis, offering new therapeutic strategies for this bone disease.
Area of Science:
- Bone biology
- Genetics
- Pharmacology
Background:
- Osteoporosis is a prevalent global health issue characterized by low bone mineral density and increased fracture risk.
- Current osteoporosis treatments have limited efficacy and significant side effects, necessitating the identification of novel therapeutic targets.
- Genetic discovery, particularly through genome-wide association studies (GWASs), is a promising avenue for identifying unbiased drug targets for osteoporosis.
Purpose of the Study:
- To review the current understanding of genetic factors influencing osteoporosis.
- To discuss strategies for identifying causal genes from GWAS loci.
- To highlight the potential of these novel genes as drug targets for osteoporosis treatment.
Main Methods:
- Review of existing literature on osteoporosis genetics and GWAS findings.
- Analysis of strategies for causal gene discovery in GWAS loci.
- Evaluation of evidence supporting novel genes as potential drug targets.
Main Results:
- Over the past decade, GWASs have identified approximately 100 loci associated with bone mineral density and fracture risk.
- Limited research has focused on identifying the causal genes within these GWAS loci and their functional mechanisms.
- Novel genes identified through GWASs represent a potential new source for osteoporosis drug targets.
Conclusions:
- Identifying causal genes and mechanisms underlying GWAS loci is crucial for advancing osteoporosis research.
- Novel genes associated with bone traits offer promising therapeutic targets for developing more effective and safer osteoporosis treatments.
- This review underscores the potential of genetic discovery in addressing the unmet needs in osteoporosis pharmacotherapy.
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