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26.11.2019 | Original Article

Targeted exon sequencing in deceased schizophrenia patients in Denmark

verfasst von: Gonçalo Espregueira Themudo, Anna-Roos Leerschool, Carla Rodriguez-Proano, Sofie Lindgren Christiansen, Jeppe Dyrberg Andersen, Johannes Rødbro Busch, Martin Roest Christensen, Jytte Banner, Niels Morling

Erschienen in: International Journal of Legal Medicine | Ausgabe 1/2020

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Abstract

Schizophrenia patients have higher mortality rates and lower life expectancy than the general population. However, forensic investigations of their deaths often fail to determine the cause of death, hindering prevention. As schizophrenia is a highly heritable condition and given recent advances in our understanding of the genetics of schizophrenia, it is now possible to investigate how genetic factors may contribute to mortality. We made use of findings from genome-wide association studies (GWAS) to design a targeted panel (PsychPlex) for sequencing of exons of 451 genes near index single nucleotide polymorphisms (SNPs) identified with GWAS. We sequenced the DNA of 95 deceased schizophrenia patients included in SURVIVE, a prospective, autopsy-based study of mentally ill persons in Denmark. We compared the allele frequencies of 1039 SNPs in these cases with the frequencies of 2000 Danes without psychiatric diseases and calculated their deleteriousness (CADD) scores. For 81 SNPs highly associated with schizophrenia and CADD scores above 15, expression profiles in the Genotype-Tissue Expression (GTEx) Project indicated that these variants were in exons, whose expressions are increased in several types of brain tissues, particularly in the cerebellum. Molecular pathway analysis indicated the involvement of 163 different pathways. As for rare SNP variants, most variants were scored as either benign or likely benign with an average of 17 variants of unknown significance per individual and no pathogenic variant. Our results highlight the potential of DNA sequencing of an exon panel to discover genetic factors that may be involved in the development of schizophrenia.

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Titel: Targeted exon sequencing in deceased schizophrenia patients in Denmark
verfasst von: Gonçalo Espregueira Themudo
Anna-Roos Leerschool
Carla Rodriguez-Proano
Sofie Lindgren Christiansen
Jeppe Dyrberg Andersen
Johannes Rødbro Busch
Martin Roest Christensen
Jytte Banner
Niels Morling
Publikationsdatum: 26.11.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: International Journal of Legal Medicine / Ausgabe 1/2020
Print ISSN: 0937-9827
Elektronische ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-019-02212-z

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Targeted exon sequencing in deceased schizophrenia patients in Denmark

Abstract

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Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

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