Manuel Mattheisen

Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Thomas W. Mühleisen, Forschungszentrum Jülich (FZJ), University Hospital and University of Basel
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  • Céline S. Reinbold, University Hospital and University of Basel
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  • Andreas J. Forstner, University Hospital Bonn, University of Bonn
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  • Lilia I. Abramova, Mental Health Research Center
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  • Martin Alda, Dalhousie University, National Institute of Mental Health
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  • Gulja Babadjanova, Russian National Research Medical University
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  • Michael Bauer, University Hospital Carl Gustav Carus
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  • Paul Brennan, International Agency for Research on Cancer
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  • Alexander Chuchalin, Russian National Research Medical University
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  • Cristiana Cruceanu, Montreal Neurological Institute, McGill University, McGill Group for Suicide Studies & Douglas Research Institute
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  • Piotr M. Czerski, Poznan University of Medical Sciences
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  • Franziska Degenhardt, University Hospital Bonn, University of Bonn
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  • Sascha B. Fischer, University Hospital and University of Basel
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  • Janice M. Fullerton, Neuroscience Research Australia, University of New South Wales (UNSW) Australia
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  • Scott D. Gordon, QIMR Berghofer Medical Research Institute
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  • Maria Grigoroiu-Serbanescu, Alexandru Obregia Clinical Psychiatric Hospital
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  • Paul Grof, The International Group for the Study of Lithium-Treated Patients (IGSLI), Mood Disorders Center of Ottawa, University of Toronto
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  • Joanna Hauser, Poznan University of Medical Sciences
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  • Martin Hautzinger, University Tübingen
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  • Stefan Herms, University Hospital and University of Basel, University Hospital Bonn, University of Bonn
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  • Per Hoffmann, University Hospital and University of Basel, University Hospital Bonn, University of Bonn
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  • Jutta Kammerer-Ciernioch, Center of Psychiatry Weinsberg
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  • Elza Khusnutdinova, Institute of Biochemistry and Genetics, Ufa Scientific Center RAS, Department of Genetics and Fundamental Medicine of Bashkir State University
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  • Manolis Kogevinas, Barcelona Institute for Global Health
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  • Valery Krasnov, Moscow Research Institute of Psychiatry
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  • André Lacour, Molecular Neuropathology of Neurodegenerative Diseases
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  • Catherine Laprise, Université du Québec à Chicoutimi, Centre intégré universitaire de santé et services sociaux du Saguenay–Lac-Saint-Jean
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  • Markus Leber, Universitat zu Koln
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  • Jolanta Lissowska, M. Sklodowska-Curie Cancer Center and Institute of Oncology
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  • Susanne Lucae, Max Planck Institute of Psychiatry
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  • Anna Maaser, University Hospital Bonn, University of Bonn
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  • Wolfgang Maier, University of Bonn
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  • Nicholas G. Martin, QIMR Berghofer Medical Research Institute
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  • Manuel Mattheisen
  • Fermin Mayoral, IBIMA-Regional University Hospital of Malaga
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  • James D. McKay, International Agency for Research on Cancer
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  • Sarah E. Medland, QIMR Berghofer Medical Research Institute
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  • Philip B. Mitchell, University of New South Wales (UNSW) Australia, Prince of Wales (and St George hospitals) Hospital
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  • Susanne Moebus, Universitat Duisburg-Essen
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  • Grant W. Montgomery, QIMR Berghofer Medical Research Institute
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  • Bertram Müller-Myhsok, Max Planck Institute of Psychiatry, Munich Cluster for Systems Neurology (SyNergy), University of Liverpool
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  • Lilijana Oruc, Clinical Center University of Sarajevo
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  • Galina Pantelejeva, Mental Health Research Center
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  • Andrea Pfennig, University Hospital Carl Gustav Carus
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  • Lejla Pojskic, Clinical Center University of Sarajevo
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  • Alexey Polonikov, Kursk State Medical University
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  • Andreas Reif, University Hospital Frankfurt
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  • Fabio Rivas, IBIMA-Regional University Hospital of Malaga
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  • Guy A. Rouleau, Montreal Neurological Institute
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  • Lorena M. Schenk, University Hospital Bonn, University of Bonn
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  • Peter R. Schofield, Neuroscience Research Australia, University of New South Wales (UNSW) Australia
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  • Markus Schwarz, Psychiatric Center Nordbaden
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  • Fabian Streit, Universität Heidelberg
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  • Jana Strohmaier, Universität Heidelberg
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  • Neonila Szeszenia-Dabrowska, Nofer Institute of Occupational Medicine
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  • Alexander S. Tiganov, Mental Health Research Center
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  • Jens Treutlein, Universität Heidelberg
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  • Gustavo Turecki, McGill University, McGill Group for Suicide Studies & Douglas Research Institute
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  • Helmut Vedder, Psychiatric Center Nordbaden
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  • Stephanie H. Witt, Universität Heidelberg
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  • Thomas G. Schulze, Ludwig-Maximilians-University München
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  • Marcella Rietschel, Universität Heidelberg
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  • Markus M. Nöthen, University Hospital Bonn, University of Bonn
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  • Sven Cichon, Forschungszentrum Jülich (FZJ), University Hospital and University of Basel, University Hospital Bonn, University of Bonn

Background Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. Methods We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Results Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (P FDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (P FDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. Limitations Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. Conclusions Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD.

Original languageEnglish
JournalJournal of Affective Disorders
Volume228
Pages (from-to)20-25
Number of pages6
ISSN0165-0327
DOIs
Publication statusPublished - 1 Mar 2018

    Research areas

  • Bipolar disorder, GRB2 events in ERBB2 signaling, NCAM signaling for neurite out-growth, Neurodevelopmental disorder, Pathway analysis

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