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Article Dans Une Revue Nature Genetics Année : 2011

Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.

Pamela Sklar (1, 2) , Stephan Ripke (2, 3) , Laura J. Scott (4) , Ole A. Andreassen (5, 6) , Sven Cichon (7, 8, 9) , Nick Craddock (10) , Howard J. Edenberg (11) , John I. Nurnberger (12, 13) , Marcella Rietschel (14) , Douglas Blackwood (15, 16) , Aiden Corvin (17) , Matthew Flickinger (4) , Weihua Guan (4) , Morten Mattingsdal (5, 18) , Andrew Mcquillin (19) , Phoenix Kwan (4) , Thomas F. Wienker (20) , Mark Daly (2, 3) , Frank Dudbridge (21) , Peter A. Holmans (10, 22) , Danyu Lin (23) , Margit Burmeister (24) , Tiffany A. Greenwood (25) , Marian L. Hamshere (10, 26) , Pierandrea Muglia (26) , Erin N. Smith (27) , Peter P. Zandi (28) , Caroline M. Nievergelt (25) , Rebecca Mckinney (25) , Paul D. Shilling (25) , Nicholas J. Schork (29) , Cinnamon S. Bloss (27) , Tatiana Foroud (12) , Daniel L. Koller (12) , Elliot S. Gershon (30) , Chunyu Liu (30) , Judith A. Badner (30) , William A. Scheftner (31) , William B. Lawson (32) , Evaristus A. Nwulia (32) , Maria Hipolito (32) , William Coryell (33) , John P. Rice (34) , William Byerley (35) , Francis J. Mcmahon (36) , Thomas G. Schulze (14, 36, 37) , Wade Berrettini (38) , Falk W. Lohoff (38) , James B. Potash (28) , Pamela B. Mahon (28) , Melvin G. Mcinnis (39) , Sebastian Zöllner (39) , Peng Zhang (39) , David W. Craig (40) , Szabocls Szelinger (40) , Thomas B. Barrett (41) , René Breuer (14) , Sandra Meier (14) , Jana Strohmaier (14) , Stephanie H. Witt (14) , Federica Tozzi (26) , Anne Farmer (42) , Peter Mcguffin (42) , John Strauss (43) , Wei Xu (44) , James L. Kennedy (45) , John B. Vincent (43) , Keith Matthews (46) , Richard Day (47) , Manuel D.C. Ferreira (2, 3, 48) , Colm O'Dushlaine (2, 3) , Roy Perlis (2, 3) , Soumya Raychaudhuri (2, 3) , Douglas Ruderfer (2, 3) , Phil L. Hyoun (2) , Jordan W. Smoller (3, 2) , Jun Li (24) , Devin Absher (49) , Robert C. Thompson (50) , Fan Guo Meng (51) , Alan F. Schatzberg (52) , William E. Bunney (50) , Jack D. Barchas (51) , Edward G. Jones (53) , Stanley J. Watson (54) , Richard M. Myers (49) , Huda Akil (54) , Michael Boehnke (4) , Kim Chambert (3) , Jennifer Moran (3) , Ed Scolnick (3) , Srdjan Djurovic (5, 55) , Ingrid Melle (5, 6) , Gunnar Morken (56, 57) , Michael Gill (10, 17) , Derek Morris (17) , Emma Quinn (1, 17) , Thomas W. Mühleisen (7, 8) , Franziska A. Degenhardt (7, 8) , Manuel Mattheisen (20, 8) , Johannes Schumacher (8) , Wolfgang Maier (58) , Michael Steffens (20) , Peter Propping (8) , Markus M. Nöthen (7, 8) , Adebayo Anjorin (19) , Nick Bass (19) , Hugh Gurling (19) , Radhika Kandaswamy (19) , Jacob Lawrence (19) , Kevin Mcghee (15, 16) , Andrew Mcintosh (15, 16) , Alan W. Mclean (15, 16) , Walter J. Muir (15, 16) , Benjamin S. Pickard (15, 16) , Gerome Breen (42, 59) , David St Clair (59) , Sian Caesar (60) , Katherine Gordon-Smith (10, 60) , Lisa Jones (60) , Christine Fraser (10) , Elaine K. Green (10) , Detelina Grozeva (10) , Ian R. Jones (10) , George Kirov (10) , Valentina Moskvina (10, 26) , Ivan Nikolov (1, 10) , Michael C. O'Donovan (1, 10) , Michael J. Owen (10) , David A. Collier (42) , Amanda Elkin (42) , Richard Williamson (42) , Allan H. Young (46, 61) , I Nicol Ferrier (46) , Kari Stefansson (62) , Hreinn Stefansson (62) , Porgeir Porgeirsson (62) , Stacy Steinberg (62) , Omar Gustafsson (62) , Sarah E. Bergen (2, 3) , Vishwajit Nimgaonkar (63) , Christina Hultman (64) , Mikael Landén (64, 65) , Paul Lichtenstein (64) , Patrick Sullivan (66) , Martin Schalling (67) , Urban Osby (67) , Lena Backlund (68) , Louise Frisén (67) , Niklas Langstrom (65) , Stéphane Jamain (69, 70, 71) , Marion Leboyer (69, 70, 71) , Bruno Etain (69, 70, 71) , Frank Bellivier (69, 70, 71) , Hannes Petursson (72) , Engilbert Sigur Sson (72) , Bertram Müller-Mysok (73) , Susanne Lucae (73) , Markus Schwarz (74) , Peter R. Schofield (75, 76) , Nick Martin (48) , Grant W. Montgomery (48) , Mark Lathrop (77) , Högni Oskarsson (78) , Michael Bauer (79) , Adam Wright (80) , Philip B. Mitchell (80) , Martin Hautzinger (81) , Andreas Reif (82) , John R. Kelsoe (25, 83) , Shaun M. Purcell (3, 2)
1 Division of Psychiatric Genomics
2 Center for Human Genetic Research
3 Stanley Center for Psychiatric Research
4 Department of Biostatistics and Center for Statistical Genetics
5 Institute of Clinical Medicine [Oslo]
6 Division of Mental Health and Addiction
7 Department of Genomics, Life and Brain Center
8 Institute of Human Genetics
9 INM-1 - Institute of Neuroscience and Medicine
10 MRC Centre for Neuropsychiatric Genetics and Genomics
11 Department of Biochemistry and Molecular Biology, Department of Medical and Molecular Genetics
12 Department of Psychiatry
13 Department of Medical and Molecular Genetics
14 Department of Genetic Epidemiology in Psychiatry [Mannhein]
15 Division of Psychiatry
16 Medical Genetics Section
17 Neuropsychiatric Genetics Research Group
18 Sorlandet Hospital HF
19 Department of Psychiatry and Behavioral Sciences
20 Department of Biomedicine and the Centre for Integrative Sequencing
21 LSHTM - London School of Hygiene and Tropical Medicine
22 Biostatistics and Bioinformatics Unit
23 Department of Biostatistics
24 Department of Human Genetics, Department of Psychiatry
25 Department of Psychiatry
26 Neurosciences Centre of Excellence in Drug Discovery
27 The Scripps Translational Science Institute and Scripps Health
28 Department of Mental Health
29 The Scripps Translational Science Institute and The Scripps Research Institute
30 McKusick-Nathans Institute of Genetic Medicine
31 Rush University Medical Center [Chicago]
32 Department of Psychiatry and Behavioral Sciences
33 Department of Psychiatry
34 WUSTL - Washington University in Saint Louis
35 Department of Psychiatry
36 Unit on the Genetic Basis of Mood and Anxiety Disorders
37 Department of Psychiatry and Psychotherapy
38 Department of Psychiatry [Philadelphia]
39 Department of Psychiatry
40 TGen - The Translational Genomics Research Institute
41 Internal Medicine
42 SGDP - Social, Genetic and Developmental Psychiatry Centre
43 Molecular Neuropsychiatry and Development Laboratory
44 Department of Biostatistics
45 Psychiatric Neurogenetics Section
46 University of Dundee School of Medicine
47 School of Neurology, Neurobiology and Psychiatry
48 Queensland Institute of Medical Research
49 HudsonAlpha Institute for Biotechnology [Huntsville, AL]
50 Department of Psychiatry and Human Behavior
51 Department of Psychiatry
52 Department of Psychiatry and Behavioral Sciences [Stanford]
53 Department of Psychiatry and Behavioral Sciences
54 Molecular Psychiatry Laboratory
55 Deparment of Medical Genetics
56 Department of Psychiatry
57 Department of Neuroscience
58 Department of Psychiatry and Psychotherapy
59 Institute of Medical Sciences
60 Department of Psychiatry, School of Clinical and Experimental Medicine
61 Institute of Mental Health
62 deCODE Genetics
63 Department of Human Genetics
64 MEB - Department of Medical Epidemiology and Biostatistics
65 Insitute of Neuroscience and Physiology
66 Medstar Research Institute
67 Department of Molecular Medicine
68 Department of Psychiatry
69 IMRB - Institut Mondor de Recherche Biomédicale
70 Service de psychiatrie
71 ENBREC - European Network of Bipolar Research Expert Centres
72 Division of Psychiatry
73 Max Planck Institute of Psychiatry
74 Psychiatric Center Nordbaden
75 Prince of Wales Medical Research Institute
76 UNSW - University of New South Wales [Sydney]
77 CNG - Centre National de Génotypage
78 Therapeia
79 Department of Psychiatry and Psychotherapy, ENBREC Group
80 School of Psychiatry
81 Department of Clinical and Developmental Psychology
82 Department of Psychiatry
83 Department of Psychiatry, Special Treatment and Evaluation Program (STEP)
Peng Zhang
Wei Xu
Kari Stefansson
  • Fonction : Auteur
Stacy Steinberg
  • Fonction : Auteur
Omar Gustafsson
  • Fonction : Auteur
Patrick Sullivan
Högni Oskarsson
  • Fonction : Auteur
Adam Wright
  • Fonction : Auteur
Andreas Reif

Résumé

We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10(-7)). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.
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Dates et versions

inserm-00634944 , version 1 (17-02-2012)

Identifiants

Citer

Pamela Sklar, Stephan Ripke, Laura J. Scott, Ole A. Andreassen, Sven Cichon, et al.. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.. Nature Genetics, 2011, 43 (10), pp.977-83. ⟨10.1038/ng.943⟩. ⟨inserm-00634944⟩
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