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Genetische Grundlagen der bipolaren Störung

Genetics of bipolar disorder

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Zusammenfassung

Die bipolare Störung (BD) ist multifaktoriell verursacht, zur Entstehung tragen sowohl genetische als auch Umweltfaktoren bei. Der Durchbruch bei der Identifizierung der verantwortlichen Gene gelang mit genomweiten Assoziationsstudien (GWAS), in denen erstmals replizierbare genetische Risikovarianten für die BD gefunden wurden. Neben den durch die GWAS identifizierten häufigen genetischen Varianten mit kleinen Effekten werden auch seltene Varianten mit höherer Penetranz zur Krankheitsentstehung beitragen. So gibt es erste Hinweise darauf, dass genomische Kopienzahlvarianten mit der Entstehung der BD assoziiert sind, ihr Beitrag zur Krankheitsentstehung ist aber geringer als bei der Schizophrenie oder dem Autismus. Die wenigen bisher bei der BD durchgeführten großflächigen Sequenzierungsstudien deuten auf eine Anreicherung seltener Varianten in zuvor mit der BD assoziierten Stoffwechselwegen und Genen hin. Im Bereich der Pharmakogenetik konnte mit einer großen internationalen GWAS erstmals ein Gen identifiziert werden, welches das individuell unterschiedliche Ansprechen auf Lithium beeinflusst. Die bisher beschriebenen Risikovarianten erklären allerdings einen zu geringen Anteil der phänotypischen Varianz, als dass sie derzeit für eine individuelle Prädiktion des Erkrankungsrisikos, des Krankheitsverlaufs oder des Ansprechens auf Medikamente genutzt werden könnten. Die genetische Forschung wird in Zukunft weitere BD-assoziierte Gene identifizieren und damit das Wissen um die biologischen Grundlagen der BD entscheidend erweitern. Die genetischen Kenntnisse werden u. a. helfen, ätiologische Subgruppen sowie diagnoseübergreifende Krankheitsmechanismen zu identifizieren.

Abstract

Bipolar disorder (BD) has a multifactorial etiology. Its development is influenced by genetic as well as environmental factors. Large genome-wide association studies (GWAS), in which genetic risk allelic variants for the disorder could be replicated for the first time, marked the breakthrough in the identification of the responsible risk genes. In addition to these common genetic variants with moderate effects identified by GWAS, rare variants with a higher penetrance are expected to play a role in disease development. The results of recent studies suggest that copy number variants might contribute to BD development, although to a lesser extent than in other psychiatric disorders, such as schizophrenia or autism. Results from the initial next generation sequencing studies indicate an enrichment of rare variants in pathways and genes that were previously found to be associated with BD. In the field of pharmacogenetics, a risk gene that influences the individual variance in the response to lithium treatment was identified for the first time in a recent large international GWAS. Currently the reported risk alleles do not sufficiently explain the phenotypic variance to be used for individual prediction of disease risk, disease course or response to medication. Future genetic research will provide important insights into the biological basis of BD by the identification of additional genes associated with BD. This knowledge of genetics will help identify potential etiological subgroups as well as cross-diagnostic disease mechanisms.

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Author information

Authors and Affiliations

  1. Institut für Psychiatrische Phänomik und Genomik (IPPG), Klinikum der Universität München, Nußbaumstraße 7, 80336, München, Deutschland

    M. Budde, K. Adorjan, S. K. Schaupp &  T. G. Schulze

  2. Institut für Humangenetik, Universitätsklinikum Bonn, Bonn, Deutschland

    A. J. Forstner & M. M. Nöthen

  3. Department of Genomics, Life & Brain Center, Universität Bonn, Bonn, Deutschland

    A. J. Forstner & M. M. Nöthen

  4. Universitäre Psychiatrische Kliniken (UPK), Universität Basel, Basel, Schweiz

    A. J. Forstner

  5. Human Genomics Research Group, Departement Biomedizin, Universität Basel, Basel, Schweiz

    A. J. Forstner

  6. Institut für medizinische Genetik und Pathologie, Universitätsspital Basel, Basel, Schweiz

    A. J. Forstner

  7. Klinik für Psychiatrie und Psychotherapie, Klinikum der Universität München, München, Deutschland

    K. Adorjan

  8. Klinik für Psychiatrie, Psychotherapie und Psychosomatik, Bezirkskrankenhaus Augsburg, Augsburg, Deutschland

    S. K. Schaupp

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  1. M. Budde
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  2. A. J. Forstner
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  3. K. Adorjan
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  5. M. M. Nöthen
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  6. T. G. Schulze
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Corresponding author

Correspondence to T. G. Schulze.

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Interessenkonflikt

M. Budde, A.J. Forstner, K. Adorjan und S.K. Schaupp geben an, dass kein Interessenkonflikt besteht. M.M. Nöthen und T.G. Schulze erhalten Drittmittel von der Deutschen Forschungsgemeinschaft (DFG; FOR2107, NO246/10–1; SCHU 1603/5–1, SCHU 1603/7–1) und dem Bundesministerium für Bildung und Forschung (BMBF; 01ZX1314A, 01ZX1314K, 01ZX1314D, 01EE1404H). M.M. Nöthen ist Mitglied des DFG-geförderten Exzellenzclusters ImmunoSensation. T.G. Schulze wird von der Dr. Lisa Oehler-Stiftung (Kassel) unterstützt.

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

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Budde, M., Forstner, A.J., Adorjan, K. et al. Genetische Grundlagen der bipolaren Störung. Nervenarzt 88, 755–759 (2017). https://doi.org/10.1007/s00115-017-0336-9

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