Manuel Mattheisen

Analysis of the influence of microRNAs in lithium response in bipolar disorder

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

DOI

  • Céline S. Reinbold, University Hospital and University of Basel, F. Hoffmann-La Roche
  • ,
  • Andreas J. Forstner, University Hospital and University of Basel, F. Hoffmann-La Roche, University Hospital Bonn, University of Bonn, University of Basel
  • ,
  • Julian Hecker, Harvard School of Public Health
  • ,
  • Janice M. Fullerton, Neuroscience Research Australia, University of New South Wales (UNSW) Australia
  • ,
  • Per Hoffmann, University Hospital and University of Basel, F. Hoffmann-La Roche, University Hospital Bonn, University of Bonn
  • ,
  • Liping Hou, National Institute of Mental Health
  • ,
  • Urs Heilbronner, Klinikum Grosshaden
  • ,
  • Franziska Degenhardt, University Hospital Bonn, University of Bonn
  • ,
  • Mazda Adli, Charite - Universitatsmedizin Berlin
  • ,
  • Kazufumi Akiyama, Dokkyo Medical University
  • ,
  • Nirmala Akula, National Institute of Mental Health
  • ,
  • Raffaella Ardau, University Hospital of Cagliari
  • ,
  • Bárbara Arias, Universitat Pompeu Fabra, Barcelona
  • ,
  • Lena Backlund, Karolinska University Hospital
  • ,
  • Antonio Benabarre, Universitat Pompeu Fabra, Barcelona
  • ,
  • Susanne Bengesser, Medical University of Graz
  • ,
  • Abesh K. Bhattacharjee, Mayo Clinic
  • ,
  • Joanna M. Biernacka, Mayo Clinic, INSERM
  • ,
  • Armin Birner, Medical University of Graz
  • ,
  • Cynthia Marie-Claire, Université Paris—Denis Diderot, University of California, San Diego
  • ,
  • Pablo Cervantes, McGill University Health Center
  • ,
  • Guo Bo Chen, The University of Queensland
  • ,
  • Hsi Chung Chen, National Taiwan University Hospital
  • ,
  • Caterina Chillotti, University Hospital of Cagliari
  • ,
  • Scott R. Clark, University of Adelaide
  • ,
  • Francesc Colom, Hospital del Mar
  • ,
  • David A. Cousins, Newcastle University, United Kingdom
  • ,
  • Cristiana Cruceanu, McGill University, Douglas Mental Health University Institute
  • ,
  • Piotr M. Czerski, Poznan University of Medical Sciences
  • ,
  • Alexandre Dayer, Geneva University Hospital
  • ,
  • Bruno Étain, Université Paris—Denis Diderot, University of California, San Diego, AP-HP Assistance Publique - Hopitaux de Paris
  • ,
  • Peter Falkai, Ludwig-Maximilians-University München
  • ,
  • Louise Frisén, Karolinska University Hospital
  • ,
  • Sébastien Gard, Hôpital Charles Perrens
  • ,
  • Julie S. Garnham, Dalhousie University
  • ,
  • Fernando S. Goes, Johns Hopkins University Hospital
  • ,
  • Paul Grof, Mood Disorders Center of Ottawa
  • ,
  • Oliver Gruber, University Medical Center Göttingen
  • ,
  • Ryota Hashimoto, Osaka University
  • ,
  • Joanna Hauser, Poznan University of Medical Sciences
  • ,
  • Stefan Herms, University Hospital and University of Basel, University Hospital Bonn, University of Bonn
  • ,
  • Stéphane Jamain, INSERM
  • ,
  • Esther Jiménez, Universitat Pompeu Fabra, Barcelona
  • ,
  • Jean Pierre Kahn, Universite de Lorraine
  • ,
  • Layla Kassem, National Institute of Mental Health
  • ,
  • Sarah Kittel-Schneider, University Hospital Frankfurt
  • ,
  • Sebastian Kliwicki, Poznan University of Medical Sciences
  • ,
  • Barbara König, Landesklinikum Neunkirchen
  • ,
  • Ichiro Kusumi, Hokkaido University Graduate School of Medicine
  • ,
  • Nina Lackner, Medical University of Graz
  • ,
  • Gonzalo Laje, National Institute of Mental Health
  • ,
  • Mikael Landén, Sahlgrenska Academy, Karolinska Institutet
  • ,
  • Catharina Lavebratt, Karolinska University Hospital
  • ,
  • Marion Leboyer, Pôle de Psychiatrie
  • ,
  • Susan G. Leckband, VA San Diego Healthcare System
  • ,
  • Carlos A.López Jaramillo, Universidad de Antioquia
  • ,
  • Glenda MacQueen, University of Calgary
  • ,
  • Mirko Manchia, Universita degli Studi di Cagliari, Dalhousie University
  • ,
  • Lina Martinsson, Karolinska Institutet
  • ,
  • Manuel Mattheisen
  • Michael J. McCarthy, VA San Diego Healthcare System
  • ,
  • Susan L. McElroy, University of Cincinnati
  • ,
  • Marina Mitjans, Universitat Pompeu Fabra, Barcelona
  • ,
  • Francis M. Mondimore, Johns Hopkins University Hospital
  • ,
  • Palmiero Monteleone, University of Salerno, Seconda Università degli Studi di Napoli
  • ,
  • Caroline M. Nievergelt, Mayo Clinic
  • ,
  • Urban Ösby, Karolinska University Hospital
  • ,
  • Norio Ozaki, Nagoya University Graduate School of Medicine
  • ,
  • Roy H. Perlis, Massachusetts General Hospital, Boston
  • ,
  • Andrea Pfennig, University Hospital Carl Gustav Carus
  • ,
  • Daniela Reich-Erkelenz, Klinikum Grosshaden
  • ,
  • Guy A. Rouleau, Montreal Neurological Institute
  • ,
  • Peter R. Schofield, University of New South Wales (UNSW) Australia, Neuroscience Research Australia
  • ,
  • K. Oliver Schubert, University of Adelaide
  • ,
  • Barbara W. Schweizer, Johns Hopkins University Hospital
  • ,
  • Florian Seemüller, Ludwig-Maximilians-University München
  • ,
  • Giovanni Severino, Universita degli Studi di Cagliari
  • ,
  • Tatyana Shekhtman, Mayo Clinic
  • ,
  • Paul D. Shilling, Mayo Clinic
  • ,
  • Kazutaka Shimoda, Dokkyo Medical University
  • ,
  • Christian Simhandl, Sigmund Freud University, Bipolar Center Wiener Neustadt
  • ,
  • Claire M. Slaney, Dalhousie University
  • ,
  • Jordan W. Smoller, Massachusetts General Hospital, Boston
  • ,
  • Alessio Squassina, Universita degli Studi di Cagliari
  • ,
  • Thomas J. Stamm, Charite - Universitatsmedizin Berlin, Medical School Brandenburg
  • ,
  • Pavla Stopkova, National Institute of Mental Health
  • ,
  • Sarah K. Tighe, University Iowa
  • ,
  • Alfonso Tortorella, Seconda Università degli Studi di Napoli
  • ,
  • Gustavo Turecki, McGill University, Douglas Mental Health University Institute
  • ,
  • Julia Volkert, University Hospital Frankfurt
  • ,
  • Stephanie H. Witt, University Medical Centre Mannheim
  • ,
  • Adam J. Wright, University of New South Wales Faculty of Medicine
  • ,
  • L. Trevor Young, The University of British Columbia
  • ,
  • Peter P. Zandi, Johns Hopkins Bloomberg School of Public Health
  • ,
  • James B. Potash, University Iowa
  • ,
  • J. Raymond DePaulo, Johns Hopkins University Hospital
  • ,
  • Michael Bauer, University Hospital Carl Gustav Carus
  • ,
  • Eva Reininghaus, Medical University of Graz
  • ,
  • Tomáš Novák, National Institute of Mental Health
  • ,
  • Jean Michel Aubry, Geneva University Hospital
  • ,
  • Mario Maj, Seconda Università degli Studi di Napoli
  • ,
  • Bernhard T. Baune, University of Adelaide
  • ,
  • Philip B. Mitchell, University of New South Wales Faculty of Medicine
  • ,
  • Eduard Vieta, Universitat Pompeu Fabra, Barcelona
  • ,
  • Mark A. Frye, INSERM
  • ,
  • Janusz K. Rybakowski, Poznan University of Medical Sciences
  • ,
  • Po Hsiu Kuo, National Taiwan University
  • ,
  • Tadafumi Kato, Riken Brain Science Institute
  • ,
  • Maria Grigoroiu-Serbanescu, Alexandru Obregia Clinical Psychiatric Hospital
  • ,
  • Andreas Reif, University Hospital Frankfurt
  • ,
  • Maria Del Zompo, Universita degli Studi di Cagliari
  • ,
  • Frank Bellivier, Université Paris—Denis Diderot, University of California, San Diego, AP-HP Assistance Publique - Hopitaux de Paris
  • ,
  • Martin Schalling, Karolinska University Hospital
  • ,
  • Naomi R. Wray, The University of Queensland
  • ,
  • John R. Kelsoe, Mayo Clinic
  • ,
  • Martin Alda, Dalhousie University, National Institute of Mental Health
  • ,
  • Francis J. McMahon, National Institute of Mental Health
  • ,
  • Thomas G. Schulze, National Institute of Mental Health, Klinikum Grosshaden, Johns Hopkins University Hospital, University Medical Center Göttingen, University Medical Centre Mannheim
  • ,
  • Marcella Rietschel, University Medical Centre Mannheim
  • ,
  • Markus M. Nöthen, University Hospital Bonn, University of Bonn
  • ,
  • Sven Cichon, University Hospital and University of Basel, University Hospital Bonn, University of Bonn, Forschungszentrum Jülich (FZJ)

Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable. Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen). Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD-associated miRNAs. However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene-based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.

Original languageEnglish
Article number207
JournalFrontiers in Psychiatry
Volume9
IssueMAY
ISSN1664-0640
DOIs
Publication statusPublished - 31 May 2018

    Research areas

  • Bipolar disorder, Common variants, Genome-wide association study, Lithium response, MicroRNA

See relations at Aarhus University Citationformats

ID: 148219840