A road map for understanding molecular and genetic determinants of osteoporosis

• Published in: Nature reviews. Endocrinology Vol. 16; no. 2; pp. 91 - 103
• Main Authors: Yang, Tie-Lin, Shen, Hui, Liu, Anqi, Dong, Shan-Shan, Zhang, Lei, Deng, Fei-Yan, Zhao, Qi, Deng, Hong-Wen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2020; Nature Publishing Group
• Subjects: 631/208/191; 631/443/63; 692/163/2743/316/801; 692/699/2743/316/801; Bone density; Bone Density - physiology; Bone mineral density; Endocrinology; Epigenomics - methods; Fractures; Fractures, Bone - genetics; Fractures, Bone - metabolism; Fractures, Bone - prevention & control; Genetic aspects; Genome-wide association studies; Genome-Wide Association Study - methods; Genomes; Genomics; Genomics - methods; Health aspects; Humans; Integration; Medicine; Medicine & Public Health; Metabolomics; Metabolomics - methods; Molecular biology; Molecular modelling; Osteoporosis; Osteoporosis - epidemiology; Osteoporosis - genetics; Osteoporosis - metabolism; Pathogenesis; Patient outcomes; Proteomics; Proteomics - methods; Review Article; China
• ISSN: 1759-5029; 1759-5037; 1759-5037
• DOI: 10.1038/s41574-019-0282-7

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. In this Review, the authors highlight findings from genome-wide association studies and studies using various omics technologies individually to identify mechanisms of osteoporosis, which is a highly heritable condition. They also summarize current studies of data integration to understand, diagnose and inform the treatment of osteoporosis. Key points Osteoporosis, which is the most common bone disorder worldwide, and its related traits (low bone mineral density and osteoporotic fracture) are highly heritable. Multiple omics technologies, including genomics, transcriptomics, epigenomics, proteomics and metabolomics, have been applied to identify the molecular factors contributing to the pathogenesis of osteoporosis. Building upon the success in single-omics discovery research, studies have integrated data from different omics levels to better elucidate the molecular and functional mechanisms for osteoporosis. Integration of omics approaches can provide a holistic road map to comprehensively illuminate the complex pathogenesis of osteoporosis and fulfil the potential of personalized disease risk prediction, intervention and treatment as well as drug development or re-purposing.