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Article Dans Une Revue Am J Hum Genet Année : 2011

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

Sven Cichon (1, 2) , Thomas W. Mühleisen (3) , Franziska A. Degenhardt (3) , Manuel Mattheisen (3) , Xavier Miro (4) , Jana Strohmaier (5) , Michael Steffens (4) , Christian Meesters (6, 4) , Stefan Herms (4) , Moritz Weingarten (4) , Lutz Priebe (4) , Britta Haenisch (4) , Michael Alexander (4) , Jennifer Vollmer (4) , René Breuer (5, 7) , Christine Schmäl (5, 7) , Peter Tessmann (4) , Susanne Moebus (8) , H.-Erich Wichmann (9, 10, 11) , Stefan Schreiber (12) , Bertram Müller-Myhsok (13) , Susanne Lucae (14) , Stéphane Jamain (15, 16, 17) , Marion Leboyer (15, 16, 17) , Frank Bellivier (15, 16, 17) , Bruno Etain (15, 18) , Chantal Henry (18, 15) , Jean-Pierre Kahn (19, 20) , Simon Heath (21) , Marian Hamshere (22, 23) , Michael C. O'Donovan (22, 23) , Michael J. Owen (23, 22) , Nick Craddock (23, 22) , Markus Schwarz (24) , Helmut Vedder (24) , Jutta Kammerer-Ciernioch (24) , Andreas Reif (25) , Johanna Sasse (26) , Michael Bauer (26) , Martin Hautzinger (27, 28) , Adam Wright (29, 30) , Philip B. Mitchell (30, 29) , Peter R. Schofield (31, 29) , Grant W. Montgomery (32) , Sarah E. Medland (32) , Scott D. Gordon (32) , Nicholas G. Martin (32) , Omar Gustafsson (33) , Ole Andreassen (34, 33) , Srdjan Djurovic (33, 35) , Engilbert Sigurdsson (36) , Stacy Steinberg (37) , Hreinn Stefansson (37) , Kari Stefansson (36, 37) , Lejla Kapur-Pojskic (38) , Liliana Oruc (38) , Fabio Rivas (39) , Fermín Mayoral (39) , Alexander Chuchalin (40) , Gulja Babadjanova (40) , Alexander S. Tiganov (40) , Galina Pantelejeva (41) , Lilia I. Abramova (41) , Maria Grigoroiu-Serbanescu (42) , Carmen C. Diaconu (43) , Piotr M. Czerski (44) , Joanna Hauser (44) , Andreas Zimmer (4) , Mark Lathrop (21) , Thomas G. Schulze (45, 46) , Thomas F. Wienker (4) , Johannes Schumacher (4) , Wolfgang Maier (4) , Peter Propping (4) , Marcella Rietschel (5, 47) , Markus M. Nöthen (48)
1 Research Center Juelich [Juelich, Germany]
2 INM-1 - Institute of Neuroscience and Medicine [Jülich]
3 Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn
4 Universität Bonn = University of Bonn
5 Department of Genetic Epidemiology in Psychiatry [Mannhein]
6 Institute of Human Genetics [Erlangen, Allemagne]
7 Central Institute of Mental Health [Mannheim]
8 Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
9 Helmholtz Zentrum München = German Research Center for Environmental Health
10 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
11 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
12 CAU - Christian-Albrechts-Universität zu Kiel = Christian-Albrechts University of Kiel = Université Christian-Albrechts de Kiel
13 MPIA - Max Planck Institute for Astronomy
14 Max Planck Institute of Psychiatry
15 IMRB - Institut Mondor de Recherche Biomédicale
16 UPEC Médecine - Université Paris-Est Créteil Val-de-Marne - Faculté de médecine
17 Pôle de Psychiatrie [Hôpital Henri Mondor]
18 Service de psychiatrie
19 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
20 Fondation FondaMental [Créteil]
21 CNG - Centre National de Génotypage
22 Cardiff University
23 Institute of Psychological Medicine and Clinical Neurosciences
24 PCN - Psychiatric Center Nordbaden [Wiesloch, Germany]
25 University of Würzburg
26 University Hospital Carl Gustav Carus [Dresden, Germany]
27 Universitätsklinikum Tübingen - University Hospital of Tübingen
28 Institute of Medical Psychology and Behavioral Neurobiology [Tübingen]
29 University of New South Wales [Kensington]
30 Prince of Wales Hospital
31 NeuRA - Neuroscience Research Australia
32 Queensland Institute of Medical Research
33 Oslo University Hospital [Oslo]
34 Institute of Clinical Medicine [Oslo]
35 UiO - University of Oslo
36 University of Iceland [Reykjavik]
37 deCODE genetics [Reykjavik]
38 UNIVERSITY OF SARAJEVO - UNIVERZITET U SARAJEVU
39 CHCH - Civil Hospital Carlos Haya [Malaga, Spain]
40 VSMU - Volgograd State Medical University [Russian Federation]
41 RAMS - Russian Academy of Medical Sciences [Moscow, Russia]
42 ERA-LEARN - Prof. Dr. Alexandru Obregia Psychiatry Hospital
43 SSNIV - Stefan S. Nicolau Institute of Virology [Bucharest, Romania]
44 PUMS - Poznan University of Medical Sciences [Poland]
45 II. Physikalisches Institut [Göttingen]
46 UMG - University Medical Center Göttingen
47 Universität Mannheim
48 Rheinische Friedrich-Wilhelms-Universität Bonn

Résumé

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.

Dates et versions

inserm-04274208 , version 1 (07-11-2023)

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Citer

Sven Cichon, Thomas W. Mühleisen, Franziska A. Degenhardt, Manuel Mattheisen, Xavier Miro, et al.. Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder. Am J Hum Genet, 2011, 88 (3), pp.372-381. ⟨10.1016/j.ajhg.2011.01.017⟩. ⟨inserm-04274208⟩
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