Bipolar Disorder: Genome-Wide Association Study Interview with:
Prof. Dr. Sven Cichon, PhD
Director, Division of Medical Genetics
University Hospital Basel
Human Genomics Research Group
Department of Biomedicine
University of Basel Basel, Switzerland What were the main findings of the study?

Answer: We have identified two new gene regions that represent pieces of the jigsaw puzzle of genetic and non-genetic factors that lead to the development of bipolar disorder. One is the gene ADCY2 (Adenylate Cyclase 2) which is involved in signal transmission within nerve cells. The other region comprises two genes, both presumably playing a role in neurodevelopmental processes (MIR2113 and POU3F2). Importantly, these results come out of the largest of these kinds of studies so far, involving altogether more than 24,000 people. Were the findings unexpected?

Answer: The exact nature of the identified genes and their involvement in bipolar disorder is new to us. We have indication from other susceptibility genes found in previous studies of bipolar disorder that both nerve cell signalling as well as neurodevelopmental processes may play a role in this common neuropsychiatric disorder. However, there are literally thousands of genes that are somehow related to these biological functions in the human brain. Our study now support the importance of these biological functions in disease development and specify more of the involved genes.  What should clinicians and patients take away from your report?

Answer: The most important message is that these kinds of studies help to understand the biological foundations of bipolar disorder. It is a long way because the disease is so complex, but step by step we are getting there. Biological knowledge of the disease will eventually be the starting point for new therapies.  What recommendations do you have for future research as a result of this study?

Answer: The recent successes in identifying genetic factors involved in bipolar disorder and other complex diseases are the result of large international collaborations. In the present study, we have joined data generated by the MooDS consortium –involving researchers from Europe, Australia, and Canada- and the largest international consortium in the field of psychiatric genetic research, the Psychiatric Genomics Consortium (PGC). This enabled us to assemble the most powerful data set to date for such a systematic genetic study. Large numbers are necessary to clearly see the minor genetic differences of individual genes between patients and controls against the ‘background noise’ of genetic differences.

It is therefore of utmost importance to continue and extend large, international collaborations involving numerous psychiatrists, geneticists and statisticians world-wide.


Genome-wide association study reveals two new risk loci for bipolar disorder


Thomas W. Mühleisen, Markus Leber, Thomas G. Schulze, Jana Strohmaier, Franziska Degenhardt, Jens Treutlein, Manuel Mattheisen, Andreas J. Forstner, Johannes Schumacher, René Breuer, Sandra Meier, Stefan Herms, Per Hoffmann, André Lacour, Stephanie H. Witt, Andreas Reif, Bertram Müller-Myhsok, Susanne Lucae, Wolfgang Maier, Markus Schwarz, Helmut Vedder, Jutta Kammerer-Ciernioch, Andrea Pfennig, Michael Bauer, Martin Hautzinger, Susanne Moebus, Lutz Priebe, Piotr M. Czerski, Joanna Hauser, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, Paul Brennan, James D. McKay, Adam Wright, Philip B. Mitchell, Janice M. Fullerton, Peter R. Schofield, Grant W. Montgomery, Sarah E. Medland, Scott D. Gordon, Nicholas G. Martin, Valery Krasnow, Alexander Chuchalin, Gulja Babadjanova, Galina Pantelejeva, Lilia I. Abramova, Alexander S. Tiganov, Alexey Polonikov, Elza Khusnutdinova, Martin Alda, Paul Grof, Guy A. Rouleau, Gustavo Turecki, Catherine Laprise, Fabio Rivas, Fermin Mayoral, Manolis Kogevinas, Maria Grigoroiu-Serbanescu, Peter Propping, Tim Becker, Marcella Rietschel, Markus M. Nöthen, Sven Cicho

Nature Communications 5, Article number:3339 doi:10.1038/ncomms4339

Published11 March 2014