Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder

Sven Cichon, Thomas W. Mühleisen, Franziska A. Degenhardt, Manuel Mattheisen, Xavier Miró, Jana Strohmaier, Michael Steffens, Christian Meesters, Stefan Herms, Moritz Weingarten, Lutz Priebe, Britta Haenisch, Michael Alexander, Jennifer Vollmer, René Breuer, Christine Schmäl, Peter Tessmann, Susanne Moebus, H. Erich Wichmann, Stefan Schreiber & 56 others Bertram Müller-Myhsok, Susanne Lucae, Stéphane Jamain, Marion Leboyer, Frank Bellivier, Bruno Etain, Chantal Henry, Jean Pierre Kahn, Simon Heath, Marian Hamshere, Michael C. O'Donovan, Michael J. Owen, Nick Craddock, Markus Schwarz, Helmut Vedder, Jutta Kammerer-Ciernioch, Andreas Reif, Johanna Sasse, Michael Bauer, Martin Hautzinger, Adam Wright, Philip B. Mitchell, Peter R. Schofield, Grant W. Montgomery, Sarah E. Medland, Scott D. Gordon, Nicholas G. Martin, Omar Gustafsson, Ole Andreassen, Srdjan Djurovic, Engilbert Sigurdsson, Stacy Steinberg, Hreinn Stefansson, Kari Stefansson, Lejla Kapur-Pojskic, Liliana Oruc, Fabio Rivas, Fermín Mayoral, Alexander Chuchalin, Gulja Babadjanova, Alexander S. Tiganov, Galina Pantelejeva, Lilia I. Abramova, Maria Grigoroiu-Serbanescu, Carmen C. Diaconu, Piotr M. Czerski, Joanna Hauser, Andreas Zimmer, Mark Lathrop, Thomas G. Schulze, Thomas F. Wienker, Johannes Schumacher, Wolfgang Maier, Peter Propping, Marcella Rietschel, Markus M. Nöthen

Research output: Contribution to journalArticle

Abstract

We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls. Eight SNPs showed nominally significant association with BD and were introduced to a meta-analysis of the GWAS and the first follow-up samples. Genetic variation in the neurocan gene (NCAN) showed genome-wide significant association with BD in 2411 patients and 3613 controls (rs1064395, p = 3.02 × 10-8; odds ratio = 1.31). In a second follow-up step, we replicated this finding in independent samples of BD, totaling 6030 patients and 31,749 controls (p = 2.74 × 10-4; odds ratio = 1.12). The combined analysis of all study samples yielded a p value of 2.14 × 10-9 (odds ratio = 1.17). Our results provide evidence that rs1064395 is a common risk factor for BD. NCAN encodes neurocan, an extracellular matrix glycoprotein, which is thought to be involved in cell adhesion and migration. We found that expression in mice is localized within cortical and hippocampal areas. These areas are involved in cognition and emotion regulation and have previously been implicated in BD by neuropsychological, neuroimaging, and postmortem studies.

Original languageEnglish (US)
Pages (from-to)372-381
Number of pages10
JournalAmerican Journal of Human Genetics
Volume88
Issue number3
DOIs
StatePublished - Mar 11 2011
Externally publishedYes

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Neurocan
Genome-Wide Association Study
Bipolar Disorder
Single Nucleotide Polymorphism
Odds Ratio
Cell Adhesion
Neuroimaging
Cognition
Genes
Cell Movement
Extracellular Matrix
Meta-Analysis
Glycoproteins
Emotions
Genome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Cichon, S., Mühleisen, T. W., Degenhardt, F. A., Mattheisen, M., Miró, X., Strohmaier, J., ... Nöthen, M. M. (2011). Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder. American Journal of Human Genetics, 88(3), 372-381. https://doi.org/10.1016/j.ajhg.2011.01.017

Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder. / Cichon, Sven; Mühleisen, Thomas W.; Degenhardt, Franziska A.; Mattheisen, Manuel; Miró, Xavier; Strohmaier, Jana; Steffens, Michael; Meesters, Christian; Herms, Stefan; Weingarten, Moritz; Priebe, Lutz; Haenisch, Britta; Alexander, Michael; Vollmer, Jennifer; Breuer, René; Schmäl, Christine; Tessmann, Peter; Moebus, Susanne; Wichmann, H. Erich; Schreiber, Stefan; Müller-Myhsok, Bertram; Lucae, Susanne; Jamain, Stéphane; Leboyer, Marion; Bellivier, Frank; Etain, Bruno; Henry, Chantal; Kahn, Jean Pierre; Heath, Simon; Hamshere, Marian; O'Donovan, Michael C.; Owen, Michael J.; Craddock, Nick; Schwarz, Markus; Vedder, Helmut; Kammerer-Ciernioch, Jutta; Reif, Andreas; Sasse, Johanna; Bauer, Michael; Hautzinger, Martin; Wright, Adam; Mitchell, Philip B.; Schofield, Peter R.; Montgomery, Grant W.; Medland, Sarah E.; Gordon, Scott D.; Martin, Nicholas G.; Gustafsson, Omar; Andreassen, Ole; Djurovic, Srdjan; Sigurdsson, Engilbert; Steinberg, Stacy; Stefansson, Hreinn; Stefansson, Kari; Kapur-Pojskic, Lejla; Oruc, Liliana; Rivas, Fabio; Mayoral, Fermín; Chuchalin, Alexander; Babadjanova, Gulja; Tiganov, Alexander S.; Pantelejeva, Galina; Abramova, Lilia I.; Grigoroiu-Serbanescu, Maria; Diaconu, Carmen C.; Czerski, Piotr M.; Hauser, Joanna; Zimmer, Andreas; Lathrop, Mark; Schulze, Thomas G.; Wienker, Thomas F.; Schumacher, Johannes; Maier, Wolfgang; Propping, Peter; Rietschel, Marcella; Nöthen, Markus M.

In: American Journal of Human Genetics, Vol. 88, No. 3, 11.03.2011, p. 372-381.

Research output: Contribution to journalArticle

Cichon, S, Mühleisen, TW, Degenhardt, FA, Mattheisen, M, Miró, X, Strohmaier, J, Steffens, M, Meesters, C, Herms, S, Weingarten, M, Priebe, L, Haenisch, B, Alexander, M, Vollmer, J, Breuer, R, Schmäl, C, Tessmann, P, Moebus, S, Wichmann, HE, Schreiber, S, Müller-Myhsok, B, Lucae, S, Jamain, S, Leboyer, M, Bellivier, F, Etain, B, Henry, C, Kahn, JP, Heath, S, Hamshere, M, O'Donovan, MC, Owen, MJ, Craddock, N, Schwarz, M, Vedder, H, Kammerer-Ciernioch, J, Reif, A, Sasse, J, Bauer, M, Hautzinger, M, Wright, A, Mitchell, PB, Schofield, PR, Montgomery, GW, Medland, SE, Gordon, SD, Martin, NG, Gustafsson, O, Andreassen, O, Djurovic, S, Sigurdsson, E, Steinberg, S, Stefansson, H, Stefansson, K, Kapur-Pojskic, L, Oruc, L, Rivas, F, Mayoral, F, Chuchalin, A, Babadjanova, G, Tiganov, AS, Pantelejeva, G, Abramova, LI, Grigoroiu-Serbanescu, M, Diaconu, CC, Czerski, PM, Hauser, J, Zimmer, A, Lathrop, M, Schulze, TG, Wienker, TF, Schumacher, J, Maier, W, Propping, P, Rietschel, M & Nöthen, MM 2011, 'Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder', American Journal of Human Genetics, vol. 88, no. 3, pp. 372-381. https://doi.org/10.1016/j.ajhg.2011.01.017
Cichon, Sven ; Mühleisen, Thomas W. ; Degenhardt, Franziska A. ; Mattheisen, Manuel ; Miró, Xavier ; Strohmaier, Jana ; Steffens, Michael ; Meesters, Christian ; Herms, Stefan ; Weingarten, Moritz ; Priebe, Lutz ; Haenisch, Britta ; Alexander, Michael ; Vollmer, Jennifer ; Breuer, René ; Schmäl, Christine ; Tessmann, Peter ; Moebus, Susanne ; Wichmann, H. Erich ; Schreiber, Stefan ; Müller-Myhsok, Bertram ; Lucae, Susanne ; Jamain, Stéphane ; Leboyer, Marion ; Bellivier, Frank ; Etain, Bruno ; Henry, Chantal ; Kahn, Jean Pierre ; Heath, Simon ; Hamshere, Marian ; O'Donovan, Michael C. ; Owen, Michael J. ; Craddock, Nick ; Schwarz, Markus ; Vedder, Helmut ; Kammerer-Ciernioch, Jutta ; Reif, Andreas ; Sasse, Johanna ; Bauer, Michael ; Hautzinger, Martin ; Wright, Adam ; Mitchell, Philip B. ; Schofield, Peter R. ; Montgomery, Grant W. ; Medland, Sarah E. ; Gordon, Scott D. ; Martin, Nicholas G. ; Gustafsson, Omar ; Andreassen, Ole ; Djurovic, Srdjan ; Sigurdsson, Engilbert ; Steinberg, Stacy ; Stefansson, Hreinn ; Stefansson, Kari ; Kapur-Pojskic, Lejla ; Oruc, Liliana ; Rivas, Fabio ; Mayoral, Fermín ; Chuchalin, Alexander ; Babadjanova, Gulja ; Tiganov, Alexander S. ; Pantelejeva, Galina ; Abramova, Lilia I. ; Grigoroiu-Serbanescu, Maria ; Diaconu, Carmen C. ; Czerski, Piotr M. ; Hauser, Joanna ; Zimmer, Andreas ; Lathrop, Mark ; Schulze, Thomas G. ; Wienker, Thomas F. ; Schumacher, Johannes ; Maier, Wolfgang ; Propping, Peter ; Rietschel, Marcella ; Nöthen, Markus M. / Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder. In: American Journal of Human Genetics. 2011 ; Vol. 88, No. 3. pp. 372-381.
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AU - Cichon, Sven

AU - Mühleisen, Thomas W.

AU - Degenhardt, Franziska A.

AU - Mattheisen, Manuel

AU - Miró, Xavier

AU - Strohmaier, Jana

AU - Steffens, Michael

AU - Meesters, Christian

AU - Herms, Stefan

AU - Weingarten, Moritz

AU - Priebe, Lutz

AU - Haenisch, Britta

AU - Alexander, Michael

AU - Vollmer, Jennifer

AU - Breuer, René

AU - Schmäl, Christine

AU - Tessmann, Peter

AU - Moebus, Susanne

AU - Wichmann, H. Erich

AU - Schreiber, Stefan

AU - Müller-Myhsok, Bertram

AU - Lucae, Susanne

AU - Jamain, Stéphane

AU - Leboyer, Marion

AU - Bellivier, Frank

AU - Etain, Bruno

AU - Henry, Chantal

AU - Kahn, Jean Pierre

AU - Heath, Simon

AU - Hamshere, Marian

AU - O'Donovan, Michael C.

AU - Owen, Michael J.

AU - Craddock, Nick

AU - Schwarz, Markus

AU - Vedder, Helmut

AU - Kammerer-Ciernioch, Jutta

AU - Reif, Andreas

AU - Sasse, Johanna

AU - Bauer, Michael

AU - Hautzinger, Martin

AU - Wright, Adam

AU - Mitchell, Philip B.

AU - Schofield, Peter R.

AU - Montgomery, Grant W.

AU - Medland, Sarah E.

AU - Gordon, Scott D.

AU - Martin, Nicholas G.

AU - Gustafsson, Omar

AU - Andreassen, Ole

AU - Djurovic, Srdjan

AU - Sigurdsson, Engilbert

AU - Steinberg, Stacy

AU - Stefansson, Hreinn

AU - Stefansson, Kari

AU - Kapur-Pojskic, Lejla

AU - Oruc, Liliana

AU - Rivas, Fabio

AU - Mayoral, Fermín

AU - Chuchalin, Alexander

AU - Babadjanova, Gulja

AU - Tiganov, Alexander S.

AU - Pantelejeva, Galina

AU - Abramova, Lilia I.

AU - Grigoroiu-Serbanescu, Maria

AU - Diaconu, Carmen C.

AU - Czerski, Piotr M.

AU - Hauser, Joanna

AU - Zimmer, Andreas

AU - Lathrop, Mark

AU - Schulze, Thomas G.

AU - Wienker, Thomas F.

AU - Schumacher, Johannes

AU - Maier, Wolfgang

AU - Propping, Peter

AU - Rietschel, Marcella

AU - Nöthen, Markus M.

PY - 2011/3/11

Y1 - 2011/3/11

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