Analysis of Genetic Factors of Sporadic Schizophrenia in Family Trios Using Whole Genome Sequencing

Abstract

Schizophrenia is a mental disorder, the hereditary nature of which has been confirmed by numerous studies. Currently, more than a hundred genetic loci associated with schizophrenia have been described, and rare variants in genes and chromosomal rearrangements associated with familial cases of the disease have also been identified. However, it is not always possible to determine the hereditary nature of the pathology, many cases of schizophrenia are sporadic, and the genetic cause of such cases remains unknown. Using whole genome sequencing data for three family trios from Russia with sporadic cases of schizophrenia, we searched for rare potentially pathogenic variants in the coding and regulatory loci of the genome, including de novo and compound mutations. The polygenic risk of schizophrenia was also assessed using common polymorphic markers. As a result of the analysis, the genetic heterogeneity of sporadic forms of schizophrenia was shown, as well as the potential role of rare substitutions in genes associated with the metabolism of glutamate and inositol phosphate in sporadic cases of schizophrenia.