Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences66684210.31857/S0016675823060024SRPBKRГЕНЕТИКА ЧЕЛОВЕКАAnalysis of Genetic Factors of Sporadic Schizophrenia in Family Trios Using Whole Genome SequencingАнализ генетических факторов спорадических случаев шизофрении в семейных трио с использованием метода полногеномного секвенированияAndreevaT. V.АндрееваТ. В.an_tati@vigg.ruAfanasievPh. A.АфанасьевФ. А.evgeny.rogaev@umassmed.eduGusevF. E.ГусевФ. Е.evgeny.rogaev@umassmed.eduPatrikeevA. D.ПатрикеевА. Д.evgeny.rogaev@umassmed.eduKunizhevaS. S.КунижеваС. С.evgeny.rogaev@umassmed.eduRogaevE. I.РогаевЕ. И.evgeny.rogaev@umassmed.eduCenter for Genetics and Genetic Technologies, Faculty of Biology, Moscow State UniversityЦентр генетики и генетических технологий, Московский государственный университет им. М.В. ЛомоносоваVavilov Institute of General Genetics, Russian Academy of SciencesИнститут общей генетики им. Н.И. Вавилова Российской академии наукCenter for Genetics and Life Science, Sirius University of Science and TechnologyЦентр генетики и наук о жизни, Научно-технологический университет “Сириус”Moscow State UniversityМосковский государственный университет им. М.В. ЛомоносоваDepartment of Psychiatry, UMass Chan Medical SchoolМедицинская школа Чан Массачусетского университета, департамент психиатрии0106202359665966926022025Copyright ©; 2023, Т.В. Андреева, Ф.А. Афанасьев, Ф.Е. Гусев, А.Д. Патрикеев, С.С. Кунижева, Е.И. РогаевCopyright ©; 2023, Т.В. Андреева, Ф.А. Афанасьев, Ф.Е. Гусев, А.Д. Патрикеев, С.С. Кунижева, Е.И. Рогаев2023Т.В. Андреева, Ф.А. Афанасьев, Ф.Е. Гусев, А.Д. Патрикеев, С.С. Кунижева, Е.И. РогаевТ.В. Андреева, Ф.А. Афанасьев, Ф.Е. Гусев, А.Д. Патрикеев, С.С. Кунижева, Е.И. Рогаевhttps://transsyst.ru/0016-6758/article/view/666842

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.

Шизофрения – распространенное психическое заболевание, наследственная природа которого подтверждена многочисленными исследованиями. В настоящее время выявлено более сотни генетических локусов, ассоциированных с шизофренией, также идентифицированы редкие варианты в генах и хромосомные перестройки, связанные с семейными случаями заболевания. Однако не всегда удается определить наследственную природу патологии, многие случаи шизофрении являются спорадическими, а генетическая причина таких случаев остается неизвестна. С использованием данных полногеномного секвенирования трех семейных трио российского происхождения со спорадическими формами шизофрении мы провели поиск редких потенциально патогенных вариантов в кодирующих и регуляторных локусах генома, включая de novo и компаундные мутации. Также провели оценку полигенного риска развития шизофрении с использованием распространенных полиморфных маркеров. В результате проведенного анализа были показаны генетическая гетерогенность спорадических форм шизофрении, а также потенциальный вклад редких замен в генах, связанных с метаболизмом глутамата и инозитолфосфата, в развитие спорадических случаев шизофрении.

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