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Independent evidence for the selective influence of GABAA receptors on one component of the bipolar disorder phenotype

Molecular Psychiatry volume 16, pages 587–589 (2011)Cite this article

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We provide independent evidence in support of a recent finding by Craddock et al.1 that variation in γ-aminobutyric acid (GABA)A receptor genes is selectively associated with one component of the bipolar disorder (BD) phenotype, that is schizophrenia-like psychotic symptoms. The support is at a system-wide level and the pattern of genetic variation was not identical to that observed in the Craddock sample.

Although the GABAergic system, the major inhibitory neurotransmission system in the central nervous system, has been implicated in the etiology of BD, genetic association findings have been inconsistent.2 One of the most strongly associated polymorphisms in the recent Wellcome Trust Case Control Consortium genome-wide association study of BD (1868 cases, 2938 controls)3 is located in the GABRB1 gene, which encodes the GABAA receptor β1 subunit. The consortium conducted a further analysis to reduce biological heterogeneity. In this second analysis, the strongest signal at this polymorphism was found in the subsample meeting Research Diagnostic Criteria4 for schizoaffective, bipolar type (SABP) (n=279). Association signals were also found in the SABP subsample at GABRA4, GABRB3, GABRA5, and GABRR3 (experiment-wide P=6.6 × 10−5). This provided strong, independent evidence in support of the hypothesis that variation in other GABAA receptor genes is associated with risk for the SABP phenotype. No association was found with schizophrenia.

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Acknowledgements

This study was supported by the German Federal Ministry of Education and Research (BMBF), within the context of the National Genome Research Network plus (NGFNplus).

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Authors and Affiliations

  1. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany

    R Breuer, J Strohmaier, S Meier, T Paul, T G Schulze & M Rietschel

  2. Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK

    M L Hamshere, M C O'Donovan & N Craddock

  3. Institute of Human Genetics, University of Bonn, Bonn, Germany

    M Mattheisen, F Degenhardt, T W Mühleisen, M M Nöthen & S Cichon

  4. Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany

    M Mattheisen, F Degenhardt, T W Mühleisen, M M Nöthen & S Cichon

  5. Institute for Medical Biometry, Informatics, and Epidemiology (IMBIE), University of Bonn, Bonn, Germany

    M Mattheisen

  6. US Department of Health and Human Services, Unit on the Genetic Basis of Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

    T G Schulze

  7. Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany

    S Cichon

  8. Department of Psychiatry, University of Bonn, Bonn, Germany

    M Rietschel

Authors
  1. R Breuer
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  2. M L Hamshere
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  3. J Strohmaier
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  4. M Mattheisen
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  5. F Degenhardt
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  6. S Meier
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  7. T Paul
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  8. M C O'Donovan
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  9. T W Mühleisen
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  10. T G Schulze
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  11. M M Nöthen
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  12. S Cichon
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  13. N Craddock
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  14. M Rietschel
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Correspondence to R Breuer.

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Breuer, R., Hamshere, M., Strohmaier, J. et al. Independent evidence for the selective influence of GABAA receptors on one component of the bipolar disorder phenotype. Mol Psychiatry 16, 587–589 (2011). https://doi.org/10.1038/mp.2010.67

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