Genome-wide association study identifies 30 loci associated with bipolar disorder - Inserm - Institut national de la santé et de la recherche médicale
Article Dans Une Revue Nature Genetics Année : 2019

Genome-wide association study identifies 30 loci associated with bipolar disorder

Eli A Stahl (1, 2) , Gerome Breen (3, 4) , Andreas J Forstner (5, 6, 7) , Andrew Mcquillin (8) , Stephan Ripke (9, 10, 11) , Vassily Trubetskoy (10) , Manuel Mattheisen (12, 13, 14, 15) , Yunpeng Wang (16) , Jonathan R I Coleman (4) , Héléna A Gaspar (4) , Christiaan A de Leeuw (17) , Stacy Steinberg (18) , Jennifer M Whitehead Pavlides (19) , Maciej Trzaskowski (19) , Enda M Byrne (4) , Tune H Pers (20) , Peter A Holmans (21) , Alexander L Richards (22) , Liam Abbott (2) , Esben Agerbo (12, 13) , Huda Akil (23) , Diego Albani (24) , Ney Alliey-Rodriguez (25) , Thomas D Als (13, 12) , Adebayo Anjorin (26) , Verneri Antilla (11) , Swapnil Awasthi (10) , Judith A Badner (27) , Marie Bækvad-Hansen (12, 28) , Jack D Barchas (29) , Nicholas Bass (8) , Michael Bauer (30, 31) , Richard Belliveau (2) , Sarah E Bergen (32) , Carsten Bøcker Pedersen (12, 13) , Erlend Bøen (33) , Marco P Boks (34) , James Boocock (35) , Monika Budde (36) , William Bunney (37) , Margit Burmeister (38) , Jonas Bybjerg-Grauholm (12, 28) , William Byerley (39) , Miquel Casas (40, 41) , Felecia Cerrato (2) , Pablo Cervantes (42) , Kimberly Chambert (2) , Alexander W Charney (1) , Danfeng Chen (2) , Claire Churchhouse (2, 11) , Toni-Kim Clarke (43) , William Coryell (44) , David W Craig (45) , Cristiana Cruceanu (42, 46) , David Curtis (47, 8) , Piotr M Czerski (48) , Anders M Dale (39) , Simone de Jong (4) , Franziska Degenhardt (6, 49) , Jurgen Del-Favero (50) , J Raymond Depaulo (51) , Srdjan Djurovic (52, 53) , Amanda L Dobbyn (1) , Ashley Dumont (2) , Torbjørn Elvsåshagen (52) , Valentina Escott-Price (22) , Chun Chieh Fan (54) , Sascha B Fischer (55, 5) , Matthew Flickinger (38) , Tatiana M Foroud (56) , Liz Forty (22) , Josef Frank (57) , Christine Fraser (22) , Nelson B Freimer (35) , Louise Frisén (15, 58) , Katrin Gade (59, 60) , Diane Gage (2) , Julie Garnham (61) , Claudia Giambartolomei (35) , Marianne Giørtz Pedersen (12, 13) , Jaqueline Goldstein (2) , Scott D Gordon (62) , Katherine Gordon-Smith (63) , Elaine K Green (64) , Melissa J Green (65, 66) , Tiffany A Greenwood (54) , Jakob Grove (13, 12) , Weihua Guan (67) , José Guzman-Parra (68) , Marian L Hamshere (22) , Martin Hautzinger (69) , Urs Heilbronner (59) , Stefan Herms (55, 6) , Maria Hipolito (70) , Per Hoffmann (55, 6) , Dominic Holland (54) , Laura Huckins (1) , Stéphane Jamain (71, 72) , Jessica S Johnson (1) , Anders Juréus (32) , Radhika Kandaswamy (4) , Robert Karlsson (32) , James L Kennedy (73, 74) , Sarah Kittel-Schneider (75) , James A Knowles (76) , Manolis Kogevinas (77) , Anna C Koller (6) , Ralph Kupka (78, 79, 80) , Catharina Lavebratt (32, 58) , Jacob Lawrence (81) , William B Lawson (70) , Markus Leber (49) , Phil H Lee (2, 11) , Shawn E Levy (82) , Jun Z Li (38) , Chunyu Liu (83) , Susanne Lucae (46) , Anna Maaser (6) , Donald J Macintyre (43) , Pamela B Mahon (51, 84) , Wolfgang Maier (6) , Lina Martinsson (32) , Steve Mccarroll (2, 85) , Peter Mcguffin (4) , Melvin G Mcinnis (38) , James D Mckay (86) , Helena Medeiros (87) , Sarah E Medland (62) , Fan Meng (38) , Lili Milani (88) , Grant W Montgomery (89) , Derek W Morris (90) , Thomas W Mühleisen (55) , Niamh Mullins (4) , Hoang Nguyen (1) , Caroline M Nievergelt (54) , Annelie Nordin Adolfsson (91) , Evaristus A Nwulia (70) , Claire O'Donovan (61) , Loes M Olde Loohuis (35) , Anil P S Ori (35) , Lilijana Oruc (92) , Urban Ösby (32) , Roy H Perlis (85, 11) , Amy Perry (63) , Andrea Pfennig (30) , James B Potash (93) , Shaun M Purcell (1, 84) , Eline J Regeer (94) , Andreas Reif (75) , Céline S Reinbold (55) , John P Rice (95) , Fabio Rivas (68) , Margarita Rivera (4, 96) , Panos Roussos (1) , Douglas M Ruderfer (43) , Euijung Ryu (97) , Cristina Sánchez-Mora (98, 41) , Alan F Schatzberg (99) , William A Scheftner (27) , Nicholas J Schork (100) , Cynthia Shannon Weickert (65) , Tatyana Shehktman (54) , Paul D Shilling (54) , Engilbert Sigurdsson (101) , Claire Slaney (61) , Olav B Smeland (52) , Janet L Sobell (102) , Christine Søholm Hansen (12) , Anne T Spijker (103) , David St Clair (104) , Michael Steffens (105) , John S Strauss (74) , Fabian Streit (57) , Jana Strohmaier (57) , Szabolcs Szelinger (106) , Robert C Thompson (107) , Thorgeir E Thorgeirsson (108) , Jens Treutlein (57) , Helmut Vedder (109) , Weiqing Wang (1) , Stanley J Watson (107) , Thomas W Weickert (65) , Stephanie H Witt (57) , Simon Xi (110) , Wei Xu (111, 74) , Allan H Young (4) , Peter Zandi (51) , Peng Zhang (51) , Sebastian Zöllner (38) , Rolf Adolfsson (91) , Ingrid Agartz (32, 33) , Martin Alda (61) , Lena Backlund (32, 58) , Bernhard T Baune (112, 113) , Frank Bellivier (114, 115) , Wade H Berrettini (116) , Joanna M Biernacka (117) , Douglas H R Blackwood (43) , Michael Boehnke (107) , Anders D Børglum (13, 12) , Aiden Corvin (118) , Nicholas Craddock (22) , Mark J Daly (2, 11) , Udo Dannlowski (113) , Tõnu Esko (2, 85, 88) , Bruno Etain (115, 119, 120, 121) , Mark Frye (117) , Janice M Fullerton (65) , Elliot S Gershon (122) , Michael Gill (118) , Fernando Goes (93) , Maria Grigoroiu-Serbanescu (123) , Joanna Hauser (48) , David M Hougaard (12) , Christina M Hultman (32) , Ian Jones (22) , Lisa A Jones (63) , René S Kahn (1) , George Kirov (22) , Mikael Landén (32, 124) , Marion Leboyer (125, 121, 126) , Cathryn M Lewis (4) , Qingqin S Li (127) , Jolanta Lissowska (128) , Nicholas G Martin (62, 89) , Fermin Mayoral (68) , Susan L Mcelroy (129) , Andrew M Mcintosh (43) , Francis J Mcmahon (130) , Ingrid Melle (52) , Andres Metspalu (88) , Philip B Mitchell (65) , Gunnar Morken (131, 132) , Ole Mors (12, 13) , Preben Bo Mortensen (12, 13) , Bertram Müller-Myhsok (46, 133) , Richard M Myers (82) , Benjamin M Neale (2, 11) , Vishwajit Nimgaonkar (134) , Merete Nordentoft (12, 135) , Markus M Nöthen (49) , Michael C O'Donovan (22) , Ketil J Oedegaard (136, 53) , Michael J Owen (22) , Sara A Paciga (137) , Carlos Pato (87) , Michele T Pato (87) , Danielle Posthuma (17, 138) , Josep Antoni Ramos-Quiroga (98, 139, 41) , Marta Ribasés (98, 139, 41) , Marcella Rietschel (57) , Guy A Rouleau (42, 140) , Martin Schalling (32, 58) , Peter R Schofield (65) , Thomas G Schulze (36, 93, 57, 130) , Alessandro Serretti (141) , Jordan W Smoller (2, 11) , Hreinn Stefansson (108) , Kari Stefansson (101, 108) , Eystein Stordal (142, 143) , Patrick F Sullivan (32, 144) , Gustavo Turecki (42) , Arne E Vaaler (145) , Eduard Vieta (146) , John B Vincent (54) , Thomas Werge (12, 135) , John I Nurnberger (56) , Naomi R Wray (89) , Arianna Di Florio (22, 144) , Howard J Edenberg (56) , Sven Cichon (55, 6) , Roel A Ophoff (35) , Laura J Scott (107) , Ole A Andreassen (52) , John Kelsoe (54) , Pamela Sklar (1)
1 MSSM - Icahn School of Medicine at Mount Sinai [New York]
2 Broad Institute [Cambridge]
3 SGDP - MRC Social, Genetic and Developmental Psychiatry Centre
4 King‘s College London
5 University Hospital Basel [Basel]
6 Universität Bonn = University of Bonn
7 Philipps Universität Marburg = Philipps University of Marburg
8 UCL - University College of London [London]
9 Stanley Center for Psychiatric Research
10 Charité - UniversitätsMedizin = Berlin University Medicine
11 Massachusetts General Hospital [Boston]
12 iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research
13 Aarhus University [Aarhus]
14 JMU - Julius-Maximilians-Universität Würzburg = University of Würzburg [Würsburg, Germany]
15 Karolinska Institute
16 NORMENT - Norwegian Centre for Mental Disorders Research [Oslo]
17 VU - Vrije Universiteit Amsterdam [Amsterdam]
18 deCODE Genetics
19 QUT - Queensland University of Technology [Brisbane]
20 Center for Biological Sequence Analysis [Lyngby]
21 Functional Genomics
22 Cardiff University
23 University of Michigan System
24 IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri" = Mario Negri Institute for Pharmacological Research
25 The University of Chicago Medicine [Chicago]
26 Royal Berkshire NHS Foundation Trust
27 Rush University Medical Center [Chicago]
28 Statens Serum Institut [Copenhagen]
29 Weill Medical College of Cornell University [New York]
30 University Hospital Carl Gustav Carus [Dresden, Germany]
31 TU Dresden - Technische Universität Dresden = Dresden University of Technology
32 Karolinska Institutet [Stockholm]
33 Diakonhjemmet Hospital
34 Utrecht Brain Center [UMC]
35 UCLA - University of California [Los Angeles]
36 LMU - Fakultät für Physik - Ludwig-Maximilians-Universität [München/Munich]
37 UC Irvine - University of California [Irvine]
38 University of Michigan [Ann Arbor]
39 UC - University of California
40 CIBER-SAM - Centro de Investigación Biomédica en Red Salud Mental [Madrid]
41 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
42 McGill University = Université McGill [Montréal, Canada]
43 Edin. - University of Edinburgh
44 University of Iowa [Iowa City]
45 TGen - The Translational Genomics Research Institute
46 Max Planck Institute of Psychiatry
47 QMUL - Queen Mary University of London
48 PUMS - Poznan University of Medical Sciences [Poland]
49 University Hospital Bonn
50 UA - University of Antwerp
51 JHU - Johns Hopkins University
52 Oslo University Hospital [Oslo]
53 UiB - University of Bergen
54 UC San Diego - University of California [San Diego]
55 Unibas - Université de Bâle = University of Basel = Basel Universität
56 Indiana University School of Medicine
57 Universität Heidelberg [Heidelberg] = Heidelberg University
58 Karolinska University Hospital [Stockholm]
59 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
60 UMG - University Medical Center Göttingen
61 Dalhousie University [Halifax]
62 QIMR Berghofer Medical Research Institute
63 Worcester State University [Worcester]
64 Plymouth University
65 UNSW - University of New South Wales [Sydney]
66 NRA - Neuroscience Research Australia [Sydney, NSW, Australia]
67 UMN - University of Minnesota System
68 Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain]
69 Eberhard Karls Universität Tübingen = University of Tübingen
70 Howard University College of Medicine [Washington, DC, USA]
71 IMRB - Institut Mondor de Recherche Biomédicale
72 U955 Inserm - UPEC - IMRB - "Neuropsychiatrie translationnelle" [Créteil]
73 Campbell Family Cancer Research Institute
74 University of Toronto
75 Frankfurt University Hospital
76 Binghamton University [SUNY]
77 ISGlobal - Instituto de Salud Global - Institute For Global Health [Barcelona]
78 VU medisch centrum
79 Department of Psychiatry, VU University Medical Center & GGZ InGeest, Amsterdam, The Netherlands
80 Altrecht, Institute for Mental Health Care
81 East London Foundation NHS Trust
82 HudsonAlpha Institute for Biotechnology [Huntsville, AL]
83 UIC - University of Illinois [Chicago]
84 Brigham and Women's Hospital [Boston]
85 HMS - Harvard Medical School [Boston]
86 Genetic Cancer Susceptibility
87 SUNY Downstate Medical Center
88 University of Tartu
89 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
90 NUI Galway - National University of Ireland [Galway]
91 Umeå University = Umeå Universitet
92 UNIVERSITY OF SARAJEVO - UNIVERZITET U SARAJEVU
93 Johns Hopkins University School of Medicine [Baltimore]
94 Bipolar Disorders Program
95 WUSTL - Washington University in Saint Louis
96 UGR - Universidad de Granada = University of Granada
97 Mayo Clinic [Rochester]
98 ISCIII - Instituto de Salud Carlos III [Madrid]
99 Stanford University
100 The Scripps Translational Science Institute and Scripps Health
101 University of Iceland [Reykjavik]
102 USC - University of Southern California
103 Mood Disorders Clinic, Dr. Jose Horwitz Psychiatric Institute,
104 University of Aberdeen
105 BfArM - Federal Institute for Drugs and Medical Devices
106 Neurogenomics, TGen [Los Angeles, USA]
107 University of Michigan [Dearborn]
108 deCODE genetics [Reykjavik]
109 Psychiatrisches Zentrum Nordbaden [Wiesloch, Germany]
110 Pfizer Global Research and Development [Cambridge, MA, USA]
111 Princess Margaret Cancer Centre [Toronto, Canada]
112 University of Melbourne
113 WWU - Westfälische Wilhelms-Universität Münster = University of Münster
114 Fondation FondaMental [Créteil]
115 OPTeN (UMR_S 1144 / U1144) - Optimisation thérapeutique en Neuropsychopharmacologie
116 University of Pennsylvania
117 Mayo Clinic
118 Trinity College Dublin
119 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London
120 UPD7 - Université Paris Diderot - Paris 7
121 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
122 University of Chicago
123 ERA-LEARN - Prof. Dr. Alexandru Obregia Psychiatry Hospital
124 Chalmers University of Technology [Gothenburg, Sweden]
125 UPE - Université Paris-Est
126 INSERM - Institut National de la Santé et de la Recherche Médicale
127 Janssen Research & Development
128 The M Sklodowska-Curie Cancer Center
129 Lindner Center of HOPE [ Mason, USA]
130 National Institute of mental health , Bethesda
131 NTNU - Norwegian University of Science and Technology [Trondheim]
132 St. Olav's University Hospital - St. Olavs Hospital HF
133 University of Liverpool
134 PITT - University of Pittsburgh
135 UCPH - University of Copenhagen = Københavns Universitet
136 Haukeland University Hospital
137 Pfizer Global Research & Development
138 Medical Center, Vrije Universiteit
139 Vall d'Hebron University Hospital [Barcelona]
140 Montreal Neurological Institute and Hospital
141 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
142 Nord University - Faculty of Nursing and Health Sciences (Namsos)
143 NTNU - Norwegian University of Science and Technology
144 UNC - University of North Carolina System
145 Trondheim University
146 UB - Universitat de Barcelona
Stacy Steinberg
  • Fonction : Auteur
Liz Forty
  • Fonction : Auteur
Lili Milani
  • Fonction : Auteur
Joanna M Biernacka
  • Fonction : Auteur
Mark Frye
  • Fonction : Auteur
Ian Jones
  • Fonction : Auteur
George Kirov
  • Fonction : Auteur

Résumé

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.
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inserm-04685993 , version 1 (03-09-2024)

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Eli A Stahl, Gerome Breen, Andreas J Forstner, Andrew Mcquillin, Stephan Ripke, et al.. Genome-wide association study identifies 30 loci associated with bipolar disorder. Nature Genetics, 2019, 51 (5), pp.793-803. ⟨10.1038/s41588-019-0397-8⟩. ⟨inserm-04685993⟩
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