Department of Economics and Business Economics

Manuel Mattheisen

Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder

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

  • A J Forstner, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • A Hofmann, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • A Maaser, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • S Sumer, Philipps-Universität Marburg, Germany
  • S Khudayberdiev, Philipps-Universität Marburg, Germany
  • T W Mühleisen, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • M Leber, University of Bonn, Germany
  • T G Schulze, Ludwig-Maximilians-Universität, München, Germany
  • J Strohmaier, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany., Germany
  • F Degenhardt, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • J Treutlein, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany., Germany
  • M Mattheisen
  • J Schumacher, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • R Breuer, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany., Germany
  • S Meier
  • ,
  • S Herms, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • P Hoffmann, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • A Lacour, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, D-53175 Bonn, Germany., Germany
  • S H Witt, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany., Germany
  • A Reif, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main, Frankfurt, Germany
  • B Müller-Myhsok, Max Planck Inst Psychiat, Max Planck Society, Germany
  • S Lucae, Max Planck Inst Psychiat, Max Planck Society, Germany
  • W Maier, Univ Bonn, University of Bonn, Dept Psychiat, Germany
  • M Schwarz, Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany., Germany
  • H Vedder, Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany., Germany
  • J Kammerer-Ciernioch, Center of Psychiatry Weinsberg, Weinsberg, Germany
  • A Pfennig, Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany., Germany
  • M Bauer, Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany., Germany
  • M Hautzinger, Department of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen, D-72074 Tübingen, Germany., Germany
  • S Moebus, Institute of Medical Informatics, Biometry, and Epidemiology, University Duisburg-Essen, D-45147 Essen, Germany., Germany
  • L Priebe, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • S Sivalingam, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • A Verhaert, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • H Schulz, University of Cologne, Germany
  • P M Czerski, Department of Psychiatry, Poznan University of Medical Sciences, Poznan PL-60-572, Poland., Poland
  • J Hauser, Department of Psychiatry, Poznan University of Medical Sciences, Poznan PL-60-572, Poland., Poland
  • J Lissowska, Marie Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology Warsaw, Department of Cancer Epidemiology and Prevention, Poland
  • N Szeszenia-Dabrowska, Department of Epidemiology, Nofer Institute of Occupational Medicine, Lodz PL-91-348, Poland., Poland
  • P Brennan, International Agency for Research on Cancer, Lyon, France., France
  • J D McKay, International Agency for Research on Cancer, Lyon, France., France
  • A Wright, The University of New South Wales, Australia
  • P B Mitchell, The University of New South Wales, Australia
  • J M Fullerton, Neuroscience Research Australia, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia., Australia
  • P R Schofield, Neuroscience Research Australia, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia., Australia
  • G W Montgomery, Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia., Australia
  • S E Medland, Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia., Australia
  • S D Gordon, Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia., Australia
  • N G Martin, Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia., Australia
  • V Krasnov, Moscow Research Institute of Psychiatry, Moscow 107258, Russian Federation., Russian Federation
  • A Chuchalin, Institute of Pulmonology, Russian State Medical University, Moscow 105077, Russian Federation., Russian Federation
  • G Babadjanova, Institute of Pulmonology, Russian State Medical University, Moscow 105077, Russian Federation., Russian Federation
  • G Pantelejeva, Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation., Russian Federation
  • L I Abramova, Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation., Russian Federation
  • A S Tiganov, Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation., Russian Federation
  • A Polonikov, Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk 305041, Russian Federation., Russian Federation
  • E Khusnutdinova, Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa 450054, Russian Federation., Russian Federation
  • M Alda, Department of Psychiatry, Dalhousie University, Halifax, NS, Canada., Canada
  • C Cruceanu, McGill University, Canada
  • G A Rouleau, McGill University, Montreal, Canada
  • G Turecki, McGill University, Montreal, Canada
  • C Laprise, Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC), Saguenay, Canada G7H 2B1., Canada
  • F Rivas, Department of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga, Spain
  • F Mayoral, Department of Psychiatry, Hospital Regional Universitario Carlos Haya, Malaga 29009, Spain., Spain
  • M Kogevinas, Center for Research in Environmental Epidemiology (CREAL), Barcelona 08003, Spain., Spain
  • M Grigoroiu-Serbanescu, Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest RO-041914, Romania., Romania
  • P Propping, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • T Becker, University of Bonn, Germany
  • M Rietschel, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany., Germany
  • S Cichon, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany
  • G Schratt, Phillipps-University Marburg, Germany
  • M M Nöthen, Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Neonatology, University of Bonn, Bonn, Germany., Germany

Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.

Original languageEnglish
JournalTranslational Psychiatry
Volume5
Pages (from-to)e678
Number of pages8
ISSN2158-3188
DOIs
Publication statusPublished - 2015

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