Multiomics approaches to search for molecular-genetic predictors of osteoporosis

Abstract

The identification of genetic loci and biochemical markers associated with the risk of fractures and the level of bone mineral density (BMD) did not give an unambiguous answer about the molecular pathogenesis of osteoporosis (OP). There are still unresolved questions about the possibility of early diagnosis and prognosis of the course of the disease. The molecular effects of genetic variants located in the coding regions of the human genome are easy to study. However, most of the single nucleotide polymorphic loci that are associated with osteoporosis susceptibility are located in non-coding or intergenic regions. Their role in the pathogenesis of this disease is not fully understood. The use of biochemical markers in the diagnosis and monitoring of osteoporosis therapy does not allow developing approaches to early diagnosis of the disease before a fracture occurs. Significant problems arise in the interpretation of research results for use in clinical medicine. But the combination of multidisciplinary data, such as genome-wide association study (GWAS), changes in the patterns of biogenic elements of bone remodeling, catalytic activity of a number of enzymes, and protein expression has significantly expanded the understanding of the key links in the pathogenesis of the disease. The article reviews and summarizes the latest advances in multiomics studies of osteoporosis, including bionformatic analysis to find key risk factors for the development of OP, as well as pharmacogenetic aspects of modern therapy of the disease.