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Article Dans Une Revue Nature Genetics Année : 2013

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Hong S. Lee (1) , Stephan Ripke (2, 3, 4) , Benjamin M. Neale (2, 3, 4) , Stephen V. Faraone (5) , Shaun M. Purcell (2, 3, 4, 6) , Roy H. Perlis (4, 7) , Bryan J. Mowry (1, 8) , Anita Thapar (9, 10) , Michael E. Goddard (11) , John S. Witte (12, 13) , Devin Absher (14) , Ingrid Agartz (15, 16) , Huda Akil (17, 18) , Farooq Amin (19) , Ole A. Andreassen (15, 20) , Adebayo Anjorin (21) , Richard Anney (22) , Verneri Anttila (2, 3) , Dan E. Arking (23) , Philip Asherson (24) , Maria H. Azevedo (25) , Lena Backlund (26) , Judith A. Badner (27) , Anthony J. Bailey (28) , Tobias Banaschewski (29) , Jack D. Barchas (30) , Michael R. Barnes (31) , Thomas B. Barrett (32) , Nicholas Bass (33, 21) , Agatino Battaglia (34) , Michael Bauer (35) , Mònica Bayés (36) , Frank Bellivier (37, 38, 39, 40) , Sarah E. Bergen (4, 2, 26) , Wade Berrettini (41) , Catalina Betancur (42, 37, 43) , Thomas Bettecken (44) , Joseph Biederman (45) , Elisabeth B. Binder (44) , Donald W. Black (46) , Douglas H. R. Blackwood (47, 48) , Cinnamon S. Bloss (49) , Michael Boehnke (17) , Dorret I. Boomsma , Gerome Breen (50, 51, 52) , René Breuer (53) , Richard Bruggeman (54) , Paul Cormican (55) , Nancy G. Buccola (56) , Jan K. Buitelaar (57) , William E. Bunney (58) , Joseph D. Buxbaum (59, 60, 61, 62, 63, 64, 65) , William F. Byerley (66) , Enda M. Byrne (1) , Sian Caesar (67) , Wiepke Cahn (61) , Rita M. Cantor (68) , Miguel Casas (61) , Aravinda Chakravarti (69, 70) , Kimberly Chambert (71) , Khalid Choudhury (72) , Sven Cichon (73, 74, 75) , Robert C. Cloninger (61) , David A. Collier (50, 52, 76) , Edwin H. Cook (77) , Hilary Coon (78) , Bru Cormand (61) , Aiden Corvin (55, 79) , William H. Coryell (80) , David W. Craig (81) , Ian W. Craig (50) , Jennifer Crosbie (81) , Michael L. Cuccaro (82) , David Curtis (83) , Darina Czamara (84) , Susmita Datta (85) , Geraldine Dawson (86) , Richard Day (87) , Eco J. de Geus (88) , Franziska Degenhardt (73, 74) , Srdjan Djurovic (89, 90) , Gary J. Donohoe (55, 91) , Alysa E. Doyle (92) , Jubao Duan (93) , Frank Dudbridge (94) , Eftichia Duketis (95) , Richard P. Ebstein (96) , Howard J. Edenberg (97) , Josephine Elia (81) , Sean Ennis (98) , Bruno Etain (99, 100) , Ayman Fanous (101) , Anne E. Farmer (50, 52) , I Nicol Ferrier (102) , Matthew Flickinger (103) , Eric Fombonne (104) , Tatiana Foroud (105) , Josef Frank (106) , Barbara Franke (106) , Christine Fraser (9, 10) , Robert Freedman (107) , Nelson B. Freimer (108) , Christine M. Freitag (95) , Marion Friedl (109) , Louise Frisén (110) , Louise Gallagher (55) , Pablo V. Gejman (93) , Lyudmila Georgieva (9, 10) , Elliot S. Gershon (111) , Daniel H. Geschwind (112) , Ina Giegling (109) , Michael Gill (55) , Scott D. Gordon (106) , Katherine Gordon-Smith (10, 67, 113) , Elaine K. Green (113) , Tiffany A. Greenwood (81) , Dorothy E. Grice (114) , Magdalena Gross (115) , Detelina Grozeva (10, 113) , Weihua Guan (103, 115) , Hugh Gurling (72) , Lieuwe de Haan (114) , Jonathan L. Haines (116) , Hakon Hakonarson (117, 118) , Joachim Hallmayer (119) , Steven P. Hamilton (120) , Marian L. Hamshere (10, 113, 121) , Thomas F. Hansen (122) , Annette M. Hartmann (109) , Martin Hautzinger (123) , Andrew C. Heath (70) , Anjali K. Henders (114) , Stefan Herms (109) , Ian B. Hickie (124) , Maria Hipolito (106) , Susanne Hoefels (114) , Peter A. Holmans (125, 10) , Florian Holsboer (126) , Witte J. Hoogendijk (127) , Jouke-Jan Hottenga (70) , Christina M. Hultman (128) , Vanessa Hus (129) , Andrés Ingason (122) , Marcus Ising (130) , Stéphane Jamain (99) , Edward G. Jones (131) , Ian Jones (9, 10) , Lisa Jones (67) , Jung-Ying Tzeng (132) , Anna K. Kähler (133) , René Sylvain Kahn (134) , Radhika Kandaswamy (135, 72) , Matthew C. Keller (133) , James L. Kennedy (136) , Elaine Kenny (55, 91) , Lindsey Kent (137) , Yunjung Kim (132) , George K. Kirov (9, 10, 138) , Sabine M. Klauck (139) , Lambertus Klei (114) , James A. Knowles (140) , Martin A. Kohli (130) , Daniel L. Koller (105) , Bettina Konte (88) , Ania Korszun (113) , Lydia Krabbendam (133) , Robert Krasucki (72) , Jonna Kuntsi (50) , Phoenix Kwan (103) , Mikael Landén (128, 141) , Niklas Långström (141) , Mark Lathrop (142) , Jacob Lawrence (135, 72) , William B. Lawson (106) , Marion Leboyer (99, 100) , David H. Ledbetter (143) , Phil H. Lee (7) , Todd Lencz (144) , Klaus-Peter Lesch (145) , Douglas F. Levinson (143) , Cathryn M. Lewis (50, 113, 146) , Jun Li (147) , Paul Lichtenstein (128) , Jeffrey A. Lieberman (145) , Dan-Yu Lin (132) , Don H. Linszen (145) , Chunyu Liu (132) , Falk W. Lohoff (41) , Sandra K. Loo (132) , Catherine Lord (129) , Jennifer K. Lowe (115) , Susanne Lucae (44) , Donald J. Macintyre (143) , Pamela A. F. Madden (88) , Elena Maestrini (148) , Patrik K. E. Magnusson (149) , Pamela B. Mahon (150) , Wolfgang Maier (149) , Anil K. Malhotra (144) , Shrikant M. Mane (151) , Christa L. Martin (152) , Nicholas G. Martin (153, 154) , Manuel Mattheisen (74, 155) , Keith Matthews (102) , Morten Mattingsdal (89, 15, 156) , Steven A. Mccarroll (71) , Kevin A. Mcghee (157, 158) , James J. Mcgough (152) , Patrick J. Mcgrath (152) , Peter Mcguffin (50, 52) , Melvin G. Mcinnis (159) , Andrew Mcintosh (157, 158) , Rebecca Mckinney (81) , Alan W. Mclean (157, 158) , Francis J. Mcmahon (160, 91) , William M. Mcmahon (78) , Andrew Mcquillin (72) , Helena Medeiros (161) , Sarah E. Medland (88) , Sandra Meier (53) , Ingrid Melle (89, 162, 15, 163) , Fan Meng (164) , Jobst Meyer (152) , Christel M. Middeldorp (70) , Lefkos Middleton (165) , Vihra Milanova (166) , Ana Miranda (167) , Anthony P. Monaco (168) , Grant W. Montgomery (153, 154) , Jennifer L. Moran (71) , Daniel Moreno-De-Luca (42) , Gunnar Morken (133, 169) , Derek W. Morris (55, 79) , Eric M. Morrow (170, 171) , Valentina Moskvina (10, 138) , Pierandrea Muglia (121) , Thomas W. Mühleisen (74, 73) , Walter J. Muir (157, 158) , Bertram Müller-Myhsok (172) , Michael Murtha (145) , Richard M. Myers (14) , Inez Myin-Germeys (44) , Michael C. Neale (101) , Stan F. Nelson (145) , Caroline M. Nievergelt (81) , Ivan Nikolov (9, 10) , Vishwajit Nimgaonkar (173) , Willem A. Nolen (174) , Markus M. Nöthen (138, 145) , John I. Nurnberger (105) , Evaristus A. Nwulia (106) , Dale R. Nyholt (88) , Colm O'Dushlaine (71) , Robert D. Oades (44) , Ann Olincy (107) , Guiomar Oliveira (175, 161) , Line Olsen (101, 122) , Roel A. Ophoff (176) , Urban Osby (110) , Michael J. Owen (9, 10) , Aarno Palotie (177) , Jeremy R. Parr (152) , Andrew D. Paterson (178, 179) , Carlos N. Pato (101) , Michele T. Pato (101) , Brenda W. Penninx (153) , Michele L. Pergadia (88) , Margaret A. Pericak-Vance (82) , Benjamin S. Pickard (157, 158) , Jonathan Pimm (72) , Joseph Piven (180) , Danielle Posthuma (125) , James B. Potash (181, 182) , Fritz Poustka (95) , Peter Propping (74) , Vinay Puri (72) , Digby J. Quested (107) , Emma M. Quinn (144, 55, 79) , Josep Antoni Ramos-Quiroga (61) , Henrik B. Rasmussen (61, 122) , Soumya Raychaudhuri (71, 183) , Karola Rehnström (184) , Andreas Reif (185) , Marta Ribasés (107) , John P. Rice (186) , Marcella Rietschel (53) , Kathryn Roeder (187) , Herbert Roeyers (188) , Lizzy Rossin (71) , Aribert Rothenberger (189) , Guy Rouleau (190) , Douglas Ruderfer (144) , Dan Rujescu (109) , Alan R. Sanders (93) , Stephan J. Sanders (191) , Susan L. Santangelo (192, 193) , Joseph A. Sergeant (194) , Russell Schachar (61) , Martin Schalling (110) , Alan F. Schatzberg (195) , William A. Scheftner (184) , Gerard D. Schellenberg (196) , Stephen W. Scherer (178, 179) , Nicholas J. Schork (197) , Thomas G. Schulze (53, 91, 181, 198) , Johannes Schumacher (74) , Markus Schwarz (199) , Edward Scolnick (71) , Laura J. Scott (103) , Jianxin Shi (200) , Paul D. Shilling (81) , Stanley I. Shyn (61) , Jeremy M. Silverman (114) , Susan L. Slager (61) , Susan L. Smalley (61) , Johannes H. Smit (153, 88) , Erin N. Smith (201) , Edmund J. S. Sonuga-Barke (143, 202) , David St Clair (51) , Matthew State (145) , Michael Steffens (155) , Hans-Christoph Steinhausen (203) , John S. Strauss (204) , Jana Strohmaier (53) , Scott T. Stroup (107) , James S. Sutcliffe (116, 205, 206) , Peter Szatmari (207) , Szabocls Szelinger (208) , Srinivasa Thirumalai (209) , Robert C. Thompson (164, 58) , Alexandre A. Todorov (210) , Federica Tozzi (121) , Jens Treutlein (184) , Manfred Uhr (130) , Edwin J. C. G. van den Oord (61) , Gerard van Grootheest (145) , Jim van Os (145) , Astrid M. Vicente (211, 212) , Veronica J. Vieland (213) , John B. Vincent (214) , Peter M. Visscher (1, 215, 216) , Christopher A. Walsh (122) , Thomas H. Wassink (217) , Stanley J. Watson (164) , Myrna M. Weissman (149) , Thomas Werge (122) , Thomas F. Wienker (109, 155) , Ellen M. Wijsman (218) , Gonneke Willemsen (153) , Nigel Williams (9, 10) , Jeremy A. Willsey (145) , Stephanie H. Witt (53) , Wei Xu (219) , Allan H. Young (102, 220) , Timothy W. Yu (61) , Stanley Zammit (9, 10) , Peter P. Zandi (221) , Peng Zhang (17) , Frans G. Zitman (88) , Sebastian Zöllner (159) , Bernie Devlin (114) , John R. Kelsoe (222, 223) , Pamela Sklar (144) , Mark J. Daly (71, 183) , Michael C. O'Donovan (9, 10) , Nicholas Craddock (10, 9) , Patrick F. Sullivan (88) , Jordan W. Smoller (71, 7) , Kenneth S. Kendler (144) , Naomi R. Wray (1)
1 Queensland Brain Institute
2 Massachusetts General Hospital [Boston]
3 HMS - Harvard Medical School [Boston]
4 BROAD INSTITUTE - Broad Institute of MIT and Harvard
5 SUNY Upstate Medical University
6 Mount Sinai School of Medicine
7 Psychiatric and Neurodevelopmental Genetics Unit
8 Queensland Centre for Mental Health Research
9 Institute of Psychological Medicine and Clinical Neurosciences
10 MRC Centre for Neuropsychiatric Genetics and Genomics
11 NSW DPI - New South Wales Department of Primary Industries
12 Faculty of Land and Food Resources
13 University of Melbourne
14 HudsonAlpha Institute for Biotechnology [Huntsville, AL]
15 Institute of Clinical Medicine [Oslo]
16 Diakonhjemmet Hospital
17 University of Michigan [Ann Arbor]
18 MBNI - Molecular and Behavioral Neuroscience Institute
19 Emory University [Atlanta, GA]
20 Oslo University Hospital [Oslo]
21 UCL - University College of London [London]
22 Trinity College Dublin
23 Johns Hopkins University School of Medicine [Baltimore]
24 MRC Social Genetic Developmental and Psychiatry Centre
25 UC - University of Coimbra [Portugal]
26 Karolinska Institutet [Stockholm]
27 University of Chicago
28 UBC - University of British Columbia
29 Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim]
30 Weill Medical College of Cornell University [New York]
31 GlaxoSmithKline
32 Portland Veterans Administration Medical Center
33 Windeyer Institute for Medical Sciences
34 IRCCS Fondazione Stella Maris [Pisa]
35 University Hospital Carl Gustav Carus [Dresden, Germany]
36 CNAG - Centro Nacional de Analisis Genomico [Barcelona]
37 INSERM - Institut National de la Santé et de la Recherche Médicale
38 UPD7 - Université Paris Diderot - Paris 7
39 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
40 ENBREC - European Network of Bipolar Research Expert Centres
41 Department of Psychiatry [Philadelphia]
42 Physiopathologie des Maladies du Système Nerveux Central
43 UPMC - Unité de recherche Phytopharmacie et Médiateurs Chimiques
44 Max Planck Institute of Psychiatry
45 Massachusetts General Hospital [Boston, MA, USA]
46 University of Iowa [Iowa City]
47 Edin. - University of Edinburgh
48 Royal Hospital for Sick Children [Edinburgh]
49 The Scripps Research Institute [La Jolla, San Diego]
50 SGDP - MRC Social, Genetic and Developmental Psychiatry Centre
51 Institute of Medical Sciences
52 SGDP - Social, Genetic and Developmental Psychiatry Centre
53 Department of Genetic Epidemiology in Psychiatry [Mannhein]
54 Department of Psychiatry
55 Department of Psychiatry
56 School of Nursing
57 Donders Center for Cognitive Neuroimaging
58 Department of Psychiatry and Human Behavior
59 Friedman Brain Institute, Mount Sinai
60 Seaver Autism Center for Research and Treatment
61 Department of Psychiatry
62 Department of Neuroscience
63 Departments of Psychiatry, Genetics and Genomic Sciences
64 Friedman Brain Institute
65 The Mindich Child Health and Development Institute
66 Department of Psychiatry
67 Department of Psychiatry, School of Clinical and Experimental Medicine
68 Department of Human Genetics, Los Angeles
69 McKusick-Nathans Institute of Genetic Medicine
70 King‘s College London
71 Stanley Center for Psychiatric Research
72 Mental Health Sciences Unit
73 Department of Genomics, Life and Brain Center
74 Institute of Human Genetics
75 INM-1 - Institute of Neuroscience and Medicine
76 Academic Department of Child and Adolescent Psychiatry, Institute of Psychiatry
77 Department of Disability and Human Development
78 Department of Developmental Neuroscience
79 Neuropsychiatric Genetics Research Group
80 Department of Psychiatry
81 Department of Psychiatry
82 John P. Hussman Institute for Human Genomics
83 East London NHS Foundation Trust
84 Max-Planck-Institut für Psychiatrie
85 Genetics Institute
86 Autism Speaks and the Department of Psychiatry
87 School of Neurology, Neurobiology and Psychiatry
88 Medstar Research Institute
89 KG Jebsen Centre for Psychosis Research
90 Deparment of Medical Genetics
91 Human Genetics Branch
92 Psychiatric and Neurodevelopmental Genetics Unit
93 Department of Psychiatry and Behavioral Sciences
94 Department of Non-Communicable Disease Epidemiology
95 Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy
96 Psychology Department
97 Department of Biochemistry and Molecular Biology, Department of Medical and Molecular Genetics
98 ACoRD - Academic Centre on Rare Diseases
99 IMRB - Institut Mondor de Recherche Biomédicale
100 Service de psychiatrie
101 Virginia Institute of Psychiatric and Behavioral Genetics
102 University of Dundee School of Medicine
103 Department of Biostatistics and Center for Statistical Genetics
104 Department of Child Psychiatry
105 Department of Psychiatry
106 Department of Psychiatry and Behavioral Sciences
107 Department of Psychiatry
108 Center for Neurobehavioral Genetics
109 Department of Genomics
110 Department of Molecular Medicine
111 Department of Psychiatry
112 Department of Neurology
113 MRC Centre for Neuropsychiatric Genetics and Genomics
114 Department of Psychiatry [Pittsburgh]
115 Fisico-Quimica Biologica
116 Vanderbilt Brain Institute
117 Department of Pediatrics
118 The Center for Applied Genomics
119 Stanford School of Medicine [Stanford]
120 Institute for Human Genetics
121 Neurosciences Centre of Excellence in Drug Discovery
122 Center for Genomic Medicine
123 Department of Clinical and Developmental Psychology
124 Clinical Research Unit
125 Functional Genomics
126 Neuronal Plasticity / Mouse Behaviour
127 Department of Psychiatry
128 MEB - Department of Medical Epidemiology and Biostatistics
129 Autism and Communicative Disorders Centre
130 Center for Human Genetic Research
131 Department of Psychiatry and Behavioral Sciences
132 Bioinformatics Research Center
133 Department of Neuroscience
134 MSSM - Icahn School of Medicine at Mount Sinai [New York]
135 Department of Psychiatry and Behavioral Sciences
136 Psychiatric Neurogenetics Section
137 School of Medicine
138 Institute of Human Genetics [Erlangen, Allemagne]
139 Division of Molecular Genome Analysis
140 Department of Ecology and Evolutionary Biology
141 Insitute of Neuroscience and Physiology
142 IG - Institut de Génomique d'Evry
143 Developmental Brain and Behaviour Unit
144 Division of Psychiatric Genomics
145 Institute of Human Genetics
146 Statistical Genetics Group
147 Department of Human Genetics
148 Department of Pharmacy and Biotechnology
149 Department of Psychiatry and Psychotherapy
150 Department of Mental Health
151 W.M. Keck Biotechnology Resource Laboratory
152 Institutes of Neuroscience and Health and Society
153 Genetic Epidemiology Unit
154 Queensland Institute of Medical Research
155 Department of Biomedicine and the Centre for Integrative Sequencing
156 Sorlandet Hospital HF
157 Division of Psychiatry
158 Medical Genetics Section
159 Department of Psychiatry
160 Unit on the Genetic Basis of Mood and Anxiety Disorders
161 UNDA - Unidade de Neurodesenvolvimento e Autismo
162 Division of Mental Health and Addiction
163 Division of Mental Health and Addiction
164 Molecular Psychiatry Laboratory
165 Research and Development
166 Department of Psychiatry
167 Registo Oncológico Regional-Sul
168 The Wellcome Trust Centre for Human Genetics [Oxford]
169 Department of Psychiatry
170 Department of Psychiatry and Human Behavior
171 Department of Molecular Biology, Cell Biology and Biochemistry
172 Translational Centre for Regenerative Medicine (TRM); Department of Cell Therapy
173 Human Genetics Department
174 Department of Psychiatry
175 Institute for Biomedical Imaging and Life Science
176 Department of Psychiatry
177 Head of Medical Sequencing
178 Program in Genetics and Genomic Biology
179 The Centre for Applied Genomics, Toronto
180 Carolina Institute for Developmental Disabilities
181 Department of Psychiatry and Behavioral Sciences
182 Department of Psychiatry
183 Analytic and Translational Genetics Unit
184 Rush University Medical Center [Chicago]
185 Department of Psychiatry
186 WUSTL - Washington University in Saint Louis
187 Department of Statistics
188 Department of Experimental Clinical and Health Psychology
189 Department of Child and Adolescent Psychiatry
190 Department of Medicine
191 Departments of Psychiatry and Genetics
192 Department of Psychiatry
193 Department of Psychiatry
194 Free University of Amsterdam
195 Department of Psychiatry and Behavioral Sciences [Stanford]
196 Pathology and Laboratory Medicine
197 The Scripps Translational Science Institute and The Scripps Research Institute
198 Department of Psychiatry and Psychotherapy
199 Psychiatric Center Nordbaden
200 Division of Cancer Epidemiology and Genetics
201 The Scripps Translational Science Institute and Scripps Health
202 Department of Experimental Clinical and Health Psychology
203 Child and Adolescent Psychiatry
204 Molecular Neuropsychiatry and Development Laboratory
205 Department of Psychiatry
206 Department of Molecular Physiology & Biophysics and Psychiatry
207 Department of Psychiatry and Behavioural Neurosciences
208 TGen - The Translational Genomics Research Institute
209 Oxford Health NHS Foundation Trust
210 Department of Psychiatry
211 INSA - Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal]
212 BioFIG
213 Battelle Center for Mathematical Medicine
214 Department of Psychiatry
215 Diamantina Institute
216 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
217 Department of Psychiatry
218 Departments of Biostatistics and Medicine
219 ArcelorMittal Maizières Research SA
220 Institute of Mental Health
221 Department of Mental Health
222 Department of Psychiatry
223 Department of Psychiatry
Dorret I. Boomsma
  • Fonction : Auteur
Darina Czamara
Susmita Datta
  • Fonction : Auteur
Eco J. de Geus
Stefan Herms
Lindsey Kent
  • Fonction : Auteur
Jun Li
Andrew Mcquillin
Andreas Reif
Guy Rouleau
Wei Xu
Peng Zhang
Naomi R. Wray
  • Fonction : Auteur correspondant
  • PersonId : 945852

Connectez-vous pour contacter l'auteur

Résumé

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
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inserm-00864642 , version 1 (28-03-2014)

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Hong S. Lee, Stephan Ripke, Benjamin M. Neale, Stephen V. Faraone, Shaun M. Purcell, et al.. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, 2013, 45 (9), pp.984-994. ⟨10.1038/ng.2711⟩. ⟨inserm-00864642⟩
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