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Genetic epidemiology of age-related osteoporosis and its clinical applications

Abstract

Osteoporosis is an important and complex disorder that is highly prevalent worldwide. This disease poses a major challenge to modern medicine and its treatment is associated with high costs. Numerous studies have endeavored to decipher the pathogenesis of this disease. The clinical assessment of patients often incorporates information about a family history of osteoporotic fractures. Indeed, the observation of an increased risk of fracture in an individual with a positive parental history of hip fracture provides strong evidence for the heritability of osteoporosis. The onset and progression of osteoporosis are generally controlled by multiple genetic and environmental factors, as well as interactions between them, with rare cases determined by a single gene. In an attempt to identify the genetic markers of complex diseases such as osteoporosis, there has been a move away from traditional linkage mapping studies and candidate gene association studies to higher-density genome-wide association studies. The advent of high-throughput technology enables genotyping of millions of DNA markers in the human genome, and consequently the identification and characterization of causal variants and loci that underlie osteoporosis. This Review presents an overview of the major findings since 2007 and clinical applications of these genome-wide linkage and association studies.

Key Points

  • Osteoporosis is a complex disease and bone mineral density (BMD) and osteoporotic fractures are highly heritable traits

  • Genetic studies using linkage and association approaches have identified a number of osteoporosis susceptibility genes and loci that are associated with low BMD and fracture risk

  • The loci identified by candidate gene association and genome-wide association studies are involved in several well-defined biological pathways related to bone metabolism

  • This genetic information has potential clinical applications in terms of nosology, risk prediction, pharmacogenetics, and the development of biomarkers and therapeutic agents

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Acknowledgements

This work was supported by the Research Grant Council of the Hong Kong Government, The Osteoporosis Research Fund and Matching Grant of the University of Hong Kong.

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C.-L. Cheung, S.-M. Xiao and A. W. C. Kung researched the data for the article. C.-L. Cheung and A. W. C. Kung provided a substantial contribution to discussion of the content and to writing the article. A. W. C. Kung reviewed and/or edited the manuscript before submission.

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Correspondence to Annie W. C. Kung.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Single nucleotide polymorphisms associated with osteoporosis and osteoporosis-related phenotypes identified in genome-wide association studies. (DOC 194 kb)

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Cheung, CL., Xiao, SM. & Kung, A. Genetic epidemiology of age-related osteoporosis and its clinical applications. Nat Rev Rheumatol 6, 507–517 (2010). https://doi.org/10.1038/nrrheum.2010.106

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