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Suche nach Risikogenen bei Schizophrenie

Search for risk genes in schizophrenia

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Zusammenfassung

Hintergrund

Die Schizophrenie stellt eine schwerwiegende psychiatrische Erkrankung mit einer Häufigkeit von 0,5–1 % in der Allgemeinbevölkerung dar. Der genetische Anteil wird auf 64–81 % geschätzt.

Fragestellung

Dieses Review fasst Hauptergebnisse zur Genetik der Schizophrenie zusammen.

Material und Methode

Es werden relevante Kopplungs- und Kandidatengenstudien sowie auch genomweite Assoziationsstudien (GWAS), Studien zu strukturellen Variationen (CNVs, „copy number variants“) und zu neuesten Sequenziertechniken (NGS, „next generation sequencing“) vorgestellt und diskutiert.

Ergebnisse

Die letzte und weltweit größte genetische Studie zur Schizophrenie zeigte 128 genomweit signifikante Polymorphismen (SNPs, „single nucleotide polymorphisms“) bzw. 108 genomweite Loci auf. Insbesondere sticht die deutlichste Assoziation mit genetischen Variationen im MHC-Bereich („major histocompatibility complex“) hervor. Zusätzlich zu Polymorphismen haben strukturelle Variationen (CNVs) in Form von Mikrodeletionen oder -duplikationen bei einer Teilgruppe der Patienten einen sehr hohen, vermutlich ursächlichen Einfluss. Hierzu zählen v. a. Mikrodeletionen auf 1q21.1, 2p16.3, 3q29, 15q13.3, 16p11.2 als auch die bereits bekannte große Deletion auf 22q11.21 sowie die Mikroduplikation auf 16p11.2.

Schlussfolgerungen

Es wird erwartet, dass die neuen Sequenzierstudien zu einem enormen weiteren Wissenszuwachs führen werden. Zukünftige Studien werden sich zudem vor allem mit der funktionellen Charakterisierung genetischer Varianten beschäftigen.

Abstract

Background

Schizophrenia is a severe psychiatric disease affecting approximately 0.5–1% of the general population. The relative contribution of genetic factors has been estimated to be 64–81%.

Objective

This review summarizes recent efforts to identify genetic variants associated with schizophrenia.

Methods

Relevant linkage and candidate genes as well as genome wide association studies, studies on copy number variants and next generation sequencing are presented and discussed.

Results

The latest and worldwide largest study on the genetics of schizophrenia found 128 genome wide significant single nucleotide polymorphisms (SNP) and 108 genome wide loci. The most obvious association is with genetic variations in the major histocompatibility complex (MHC). Besides polymorphisms, structural variants in the form of copy number variants (CNV), such as microdeletions and microduplications have a very high impact in a subgroup of patients. These CNVs are mainly microdeletions on 1q21.1, 2p16.3, 3q29, 15q13.3 and 16p11.2 as well as a large deletion on 22q11.21 and a microduplication on 16p11.2.

Conclusion

A large new body of evidence on the genetics of schizophrenia is expected through next generation sequencing approaches. Future studies will particularly address the functional characterization of genetic variants.

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Authors and Affiliations

  1. Klinik und Poliklinik für Psychiatrie, Psychotherapie und Psychosomatik, Martin-Luther-Universität Halle-Wittenberg, Julius-Kühn-Str. 7, 06112, Halle, Deutschland

    D. Rujescu

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Correspondence to D. Rujescu.

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D. Rujescu gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Rujescu, D. Suche nach Risikogenen bei Schizophrenie. Nervenarzt 88, 751–754 (2017). https://doi.org/10.1007/s00115-017-0330-2

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