The role of ROH in the etiopathogenesis of complex diseases

Abstract

Aim. To carry out a comparative analysis of the main directions of genetic studies of complex (chronic) human neuropsychiatric diseases and to determine the prospects for their genomic studies.Discussion. Complex diseases account for more than 90% of the total human pathology and are the main cause of premature death and disability. One of the most urgent and severe categories of complex diseases, both for the patients themselves and for society, are endogenous mental illnesses, in particular, schizophrenia, mental retardation and autism spectrum disorders. Despite the fact that genetic and epidemiological studies show high heritability rates (up to 70‐80%), the identification of predisposition genes remains a challenge. Studies in recent decades have contributed to understanding the genetic mechanisms of the pathogenesis of such diseases and have significantly advanced our understanding in terms of identifying risk loci, possible mechanisms for the transmission of genetic risk, and the involvement in the pathogenesis of such diseases of not one but of a large number of genes that provide many variants of gene expression. However, the mapping of genes that control such clinical phenotypes and mutations in them that cause pathogenesis remains largely unknown.Conclusion. The finding of the same gene changes in neuropsychiatric complex diseases suggests that the genes involved converge in biochemical pathways and may be caused by a complex interplay of genetic and environmental factors characterized by genetic heterogeneity, which is often associated with clinical heterogeneity, incomplete penetrance and phenocopies. This is of great importance for the development of gene therapy through the identification of drug targets for the treatment of these disorders.