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 Cichon

doi:10.1038/ncomms4339

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 SchwarzHelmut 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 Cichon

Research output: Contribution to journal › Article › peer-review

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Abstract

Bipolar disorder (BD) is a common and highly heritable mental illness and genome-wide association studies (GWAS) have robustly identified the first common genetic variants involved in disease aetiology. The data also provide strong evidence for the presence of multiple additional risk loci, each contributing a relatively small effect to BD susceptibility. Large samples are necessary to detect these risk loci. Here we present results from the largest BD GWAS to date by investigating 2.3 million single-nucleotide polymorphisms (SNPs) in a sample of 24,025 patients and controls. We detect 56 genome-wide significant SNPs in five chromosomal regions including previously reported risk loci ANK3, ODZ4 and TRANK1, as well as the risk locus ADCY2 (5p15.31) and a region between MIR2113 and POU3F2 (6q16.1). ADCY2 is a key enzyme in cAMP signalling and our finding provides new insights into the biological mechanisms involved in the development of BD.

Original language	English (US)
Article number	3339
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms4339
State	Published - Mar 11 2014
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
General Chemistry
General Physics and Astronomy
General Medicine

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10.1038/ncomms4339

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Mühleisen, T. W., Leber, M., Schulze, T. G., Strohmaier, J., Degenhardt, F., Treutlein, J., Mattheisen, M., Forstner, A. J., Schumacher, J., Breuer, R., Meier, S., Herms, S., Hoffmann, P., Lacour, A., Witt, S. H., Reif, A., Müller-Myhsok, B., Lucae, S., Maier, W., ... Cichon, S. (2014). Genome-wide association study reveals two new risk loci for bipolar disorder. Nature Communications, 5, Article 3339. https://doi.org/10.1038/ncomms4339

Mühleisen, TW, Leber, M, Schulze, TG, Strohmaier, J, Degenhardt, F, Treutlein, J, Mattheisen, M, Forstner, AJ, Schumacher, J, Breuer, R, Meier, S, Herms, S, Hoffmann, P, Lacour, A, Witt, SH, Reif, A, Müller-Myhsok, B, Lucae, S, Maier, W, Schwarz, M, Vedder, H, Kammerer-Ciernioch, J, Pfennig, A, Bauer, M, Hautzinger, M, Moebus, S, Priebe, L, Czerski, PM, Hauser, J, Lissowska, J, Szeszenia-Dabrowska, N, Brennan, P, McKay, JD, Wright, A, Mitchell, PB, Fullerton, JM, Schofield, PR, Montgomery, GW, Medland, SE, Gordon, SD, Martin, NG, Krasnow, V, Chuchalin, A, Babadjanova, G, Pantelejeva, G, Abramova, LI, Tiganov, AS, Polonikov, A, Khusnutdinova, E, Alda, M, Grof, P, Rouleau, GA, Turecki, G, Laprise, C, Rivas, F, Mayoral, F, Kogevinas, M, Grigoroiu-Serbanescu, M, Propping, P, Becker, T, Rietschel, M, Nöthen, MM & Cichon, S 2014, 'Genome-wide association study reveals two new risk loci for bipolar disorder', Nature Communications, vol. 5, 3339. https://doi.org/10.1038/ncomms4339

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title = "Genome-wide association study reveals two new risk loci for bipolar disorder",

abstract = "Bipolar disorder (BD) is a common and highly heritable mental illness and genome-wide association studies (GWAS) have robustly identified the first common genetic variants involved in disease aetiology. The data also provide strong evidence for the presence of multiple additional risk loci, each contributing a relatively small effect to BD susceptibility. Large samples are necessary to detect these risk loci. Here we present results from the largest BD GWAS to date by investigating 2.3 million single-nucleotide polymorphisms (SNPs) in a sample of 24,025 patients and controls. We detect 56 genome-wide significant SNPs in five chromosomal regions including previously reported risk loci ANK3, ODZ4 and TRANK1, as well as the risk locus ADCY2 (5p15.31) and a region between MIR2113 and POU3F2 (6q16.1). ADCY2 is a key enzyme in cAMP signalling and our finding provides new insights into the biological mechanisms involved in the development of BD.",

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

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AU - Mühleisen, Thomas W.

AU - Leber, Markus

AU - Schulze, Thomas G.

AU - Strohmaier, Jana

AU - Degenhardt, Franziska

AU - Treutlein, Jens

AU - Mattheisen, Manuel

AU - Forstner, Andreas J.

AU - Schumacher, Johannes

AU - Breuer, René

AU - Meier, Sandra

AU - Herms, Stefan

AU - Hoffmann, Per

AU - Lacour, André

AU - Witt, Stephanie H.

AU - Reif, Andreas

AU - Müller-Myhsok, Bertram

AU - Lucae, Susanne

AU - Maier, Wolfgang

AU - Schwarz, Markus

AU - Vedder, Helmut

AU - Kammerer-Ciernioch, Jutta

AU - Pfennig, Andrea

AU - Bauer, Michael

AU - Hautzinger, Martin

AU - Moebus, Susanne

AU - Priebe, Lutz

AU - Czerski, Piotr M.

AU - Hauser, Joanna

AU - Lissowska, Jolanta

AU - Szeszenia-Dabrowska, Neonila

AU - Brennan, Paul

AU - McKay, James D.

AU - Wright, Adam

AU - Mitchell, Philip B.

AU - Fullerton, Janice M.

AU - Schofield, Peter R.

AU - Montgomery, Grant W.

AU - Medland, Sarah E.

AU - Gordon, Scott D.

AU - Martin, Nicholas G.

AU - Krasnow, Valery

AU - Chuchalin, Alexander

AU - Babadjanova, Gulja

AU - Pantelejeva, Galina

AU - Abramova, Lilia I.

AU - Tiganov, Alexander S.

AU - Polonikov, Alexey

AU - Khusnutdinova, Elza

AU - Alda, Martin

AU - Grof, Paul

AU - Rouleau, Guy A.

AU - Turecki, Gustavo

AU - Laprise, Catherine

AU - Rivas, Fabio

AU - Mayoral, Fermin

AU - Kogevinas, Manolis

AU - Grigoroiu-Serbanescu, Maria

AU - Propping, Peter

AU - Becker, Tim

AU - Rietschel, Marcella

AU - Nöthen, Markus M.

AU - Cichon, Sven

PY - 2014/3/11

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N2 - Bipolar disorder (BD) is a common and highly heritable mental illness and genome-wide association studies (GWAS) have robustly identified the first common genetic variants involved in disease aetiology. The data also provide strong evidence for the presence of multiple additional risk loci, each contributing a relatively small effect to BD susceptibility. Large samples are necessary to detect these risk loci. Here we present results from the largest BD GWAS to date by investigating 2.3 million single-nucleotide polymorphisms (SNPs) in a sample of 24,025 patients and controls. We detect 56 genome-wide significant SNPs in five chromosomal regions including previously reported risk loci ANK3, ODZ4 and TRANK1, as well as the risk locus ADCY2 (5p15.31) and a region between MIR2113 and POU3F2 (6q16.1). ADCY2 is a key enzyme in cAMP signalling and our finding provides new insights into the biological mechanisms involved in the development of BD.

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

Abstract

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