Candidate Genetic Markers of Schizophrenia Based on Exome Sequencing Data and Its Relation to Immunological, Clinical, and Morphometric Changes in the Russian Population

The aim of the study was to identify genetic markers of schizophrenia based on exome sequencing data, as well as to specify its potential relation to clinical manifestations of the disease, morphological changes in the brain and immune disorders.

Materials and Methods. The analyzed sample consisted of 48 patients (23 men and 25 women; average age — 31.5±7.7 years) having a confirmed diagnosis of paranoid schizophrenia.

Results. 140 genes with differential polymorphisms and enriched categories that may be related to the pathogenesis of schizophrenia were identified. Analysis of genes with differential frequencies of functionally significant common single nucleotide polymorphisms (SNPs) by their major functions showed that the most common were genes involved in regulation of immune system functions and development of the nervous system, as well as genes being structural components of neurons and glia involved in the perception of sensory stimuli. The findings confirm the complexity of the genetic basis of schizophrenia. Analysis of the top 10 genes containing the most differential polymorphisms specifies such genes related to schizophrenia as MUC12 and SH3KBP1. The genes involved in regulation of the immune response include HLA-DQB2 which is one of the most significantly different SNPs between the group of patients and the general population; HLA-DQB2 SNP (rs9276572) in patients is related to the signs of dysfunction of the antiviral component of immune system, structural changes in the brain and cognitive challenges. Although most of the detected genes are unique to the sample studied, additional studies are required to confirm these genes’ involvement in the pathogenesis of this disease as well as to identify the mechanisms of the disease onset and development. The rs9276572(C) polymorphism of HLA-DQB2 requires further study as a new potential marker of immunological disorders, morphometric changes in the brain and cognitive impairment in schizophrenia. The data obtained indicate the need for personalized medicine, because the majority of genetic prerequisites are patient-specific and highlight the importance of further research to understand the genetic aspects of schizophrenia and develop innovative approaches to its diagnosis and treatment.

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