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

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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.

About the authors

T. V. Andreeva

Center for Genetics and Genetic Technologies, Faculty of Biology,
Moscow State University; Vavilov Institute of General Genetics, Russian Academy of Sciences

Author for correspondence.
Email: an_tati@vigg.ru
Russia, 119234, Moscow; Russia, 119991, Moscow

Ph. A. Afanasiev

Vavilov Institute of General Genetics, Russian Academy of Sciences

Email: evgeny.rogaev@umassmed.edu
Russia, 119991, Moscow

F. E. Gusev

Vavilov Institute of General Genetics, Russian Academy of Sciences; Center for Genetics and Life Science, Sirius University of Science and Technology

Email: evgeny.rogaev@umassmed.edu
Russia, 119991, Moscow; Russia, 354340, Krasnodarski Krai, p. Sirius

A. D. Patrikeev

Vavilov Institute of General Genetics, Russian Academy of Sciences

Email: evgeny.rogaev@umassmed.edu
Russia, 119991, Moscow

S. S. Kunizheva

Vavilov Institute of General Genetics, Russian Academy of Sciences; Center for Genetics and Life Science, Sirius University of Science and Technology

Email: evgeny.rogaev@umassmed.edu
Russia, 119991, Moscow; Russia, 354340, Krasnodarski Krai, p. Sirius

E. I. Rogaev

Center for Genetics and Life Science, Sirius University of Science and Technology; Moscow State University; Department of Psychiatry, UMass Chan Medical School

Author for correspondence.
Email: evgeny.rogaev@umassmed.edu
Russia, 354340, Krasnodarski Krai, p. Sirius; Russia, 119234, Moscow; USA, MA 01545, Worcester

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Copyright (c) 2023 Т.В. Андреева, Ф.А. Афанасьев, Ф.Е. Гусев, А.Д. Патрикеев, С.С. Кунижева, Е.И. Рогаев

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