A road map for understanding molecular and genetic determinants of osteoporosis

Osteoporosis is a highly prevalent disorder characterized by low bone mineral density and an increased risk of fracture, termed osteoporotic fracture. Notably, bone mineral density, osteoporosis and osteoporotic fracture are highly heritable; however, determining the genetic architecture, and especi...

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Veröffentlicht in:Nature reviews. Endocrinology Jg. 16; H. 2; S. 91 - 103
Hauptverfasser: Yang, Tie-Lin, Shen, Hui, Liu, Anqi, Dong, Shan-Shan, Zhang, Lei, Deng, Fei-Yan, Zhao, Qi, Deng, Hong-Wen
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Nature Publishing Group 01.02.2020
Schlagworte:
Bone density
Bone Density - physiology
Bone mineral density
Epigenomics - methods
Fractures
Fractures, Bone - genetics
Fractures, Bone - metabolism
Fractures, Bone - prevention & control
Genome-wide association studies
Genome-Wide Association Study - methods
Genomes
Genomics
Genomics - methods
Humans
Integration
Metabolomics
Metabolomics - methods
Molecular modelling
Osteoporosis
Osteoporosis - epidemiology
Osteoporosis - genetics
Osteoporosis - metabolism
Pathogenesis
Proteomics
Proteomics - methods
ISSN:1759-5029, 1759-5037, 1759-5037
Online-Zugang:Volltext
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Zusammenfassung:Osteoporosis is a highly prevalent disorder characterized by low bone mineral density and an increased risk of fracture, termed osteoporotic fracture. Notably, bone mineral density, osteoporosis and osteoporotic fracture are highly heritable; however, determining the genetic architecture, and especially the underlying genomic and molecular mechanisms, of osteoporosis in vivo in humans is still challenging. In addition to susceptibility loci identified in genome-wide association studies, advances in various omics technologies, including genomics, transcriptomics, epigenomics, proteomics and metabolomics, have all been applied to dissect the pathogenesis of osteoporosis. However, each technology individually cannot capture the entire view of the disease pathology and thus fails to comprehensively identify the underlying pathological molecular mechanisms, especially the regulatory and signalling mechanisms. A change to the status quo calls for integrative multi-omics and inter-omics analyses with approaches in 'systems genetics and genomics'. In this Review, we highlight findings from genome-wide association studies and studies using various omics technologies individually to identify mechanisms of osteoporosis. Furthermore, we summarize current studies of data integration to understand, diagnose and inform the treatment of osteoporosis. The integration of multiple technologies will provide a road map to illuminate the complex pathogenesis of osteoporosis, especially from molecular functional aspects, in vivo in humans.
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ISSN:1759-5029
1759-5037
1759-5037
DOI:10.1038/s41574-019-0282-7