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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data

Paul M. Thompson ^{1, 2, *} Jason L. Stein ³ Sarah Medland ⁴ Derrek D Hibar ² Alejandro Arias Vasquez ⁵ Miguel E. Renteria ⁴ Roberto Toro ⁶ Neda Jahanshad ² Gunter Schumann ⁷ Barbara Franke ⁵ Margaret J. Wright ⁴ Nicholas G. Martin ⁴ Ingrid Agartz ^{8, 9, 10} Martin Alda ¹¹ Saud Alhusaini ^{12, 13} Laura Almasy ¹⁴ Jorge Almeida ^{11, 15} Kathryn Alpert ¹⁶ Nancy C. Andreasen ¹⁷ Ole A. Andreassen ^{18, 19} Liana G. Apostolova ³ Katja Appel ^{20, 21} Nicola J. Armstrong ²² Benjamin Aribisala ^{23, 24} Mark E. Bastin ^{23, 24} Michael Bauer ²⁵ Carrie E. Bearden ²⁶ Ørjan Bergmann ²⁷ Elisabeth B. Binder ²⁸ John Blangero ¹⁴ Henry J. Bockholt ¹⁷ Erlend Bøen ^{27, 18} Catherine Bois ^{29, 23} Dorret I. Boomsma ^{30, 31} Tom Booth ³² Ian J. Bowman ³³ Janita Bralten ^{34, 5} Rachel M. Brouwer ^{35, 36} Han G. Brunner ^{5, 37} David G. Brohawn ^{38, 39} Randy L. Buckner ^{40, 41} Jan Buitelaar ^{42, 34} Kazima M Bulayeva ^{43, 44} Juan R. Bustillo ⁴⁵ Vince D. Calhoun ^{46, 47} Dara M. Cannon ⁴⁸ Rita M. Cantor ^{49, 50} Melanie A. Carless ¹⁴ Xavier Caseras ⁵¹ Gianpiero L. Cavalleri ¹² M. Mallar Chakravarty ^{52, 53} Kiki D. Chang ⁵⁴ Christopher R. K. Ching ³³ Andrea Christoforou ^{19, 55} Sven Cichon ^{56, 57, 58} Vincent P. Clark ⁴⁵ Patricia Conrod ^{7, 59} Giovanni Coppola ^{26, 3} Benedicto Crespo-Facorro ^{60, 61} Joanne E Curran ¹⁴ Michael Czisch ²⁸ Ian J. Deary ⁶² Eco J. C. de Geus ^{30, 31} Anouk den Braber ³⁰ Giuseppe Delvecchio ⁷ Chantal Depondt ⁶³ Lieuwe de Haan ³¹ Greig I. de Zubicaray ⁶⁴ Danai Dima ⁷ Rali Dimitrova ^{29, 23} Srdjan Djurovic ^{8, 19, 18} Hongwei Dong ³³ Gary Donohoe ^{48, 65} Ravindranath Duggirala ¹⁴ Thomas D. Dyer ¹⁴ Stefan Ehrlich ^{66, 67} Carl Johan Ekman ^{9, 10} Torbjørn Elvsåshagen ^{27, 18} Louise Emsell ⁴⁸ Susanne Erk ⁶⁸ Thomas Espeseth ¹⁹ Jesen Fagerness ⁶⁶ Scott Fears ²⁶ Iryna Fedko ³⁰ Guillén Fernández ^{34, 5} Simon E. Fisher ^{34, 69} Tatiana Foroud ⁷⁰ Peter T. Fox ^{71, 72} Clyde Francks ^{69, 34} Sophia D Frangou ⁷³ Eva Maria Frey ⁷⁴ Thomas Frodl ^{74, 65} Vincent Frouin ⁷⁵ Hugh Garavan ⁷⁶ Sudheer Giddaluru ^{77, 55} David C. Glahn ^{78, 79} Beata Godlewska ⁸⁰ Rita Z. Goldstein ⁸¹ Randy L. Gollub ^{82, 66} Hans J. Grabe ^{20, 83, 84, 21} Oliver Grimm ⁸⁵ Oliver Gruber ⁸⁶ Tulio Guadalupe ^{87, 69} Raquel E. Gur ⁸⁸ Ruben C. Gur ⁸⁸ Harald H. H. Göring ¹⁴ Saskia Hagenaars ^{29, 23} Tomas Hajek ¹¹ Geoffrey B. Hall ⁸⁹ Jérémy Hall ^{23, 29} John Hardy ⁹⁰ Catharina A. Hartman ⁹¹ Johanna Hass ⁶⁷ Sean N. Hatton ⁹² Unn K. Haukvik ^{93, 19} Katrin Hegenscheid ^{20, 21} Andreas Heinz ⁶⁸ Ian B. Hickie ⁹² Beng-Choon Ho ¹⁷ David Hoehn ²⁸ Pieter J. Hoekstra ⁹¹ Marisa Hollinshead ^{39, 41} Avram J. Holmes ^{39, 41} Georg Homuth ^{20, 21} Martine Hoogman ⁵ L. Elliot Hong ⁹⁴ Norbert Hosten ^{20, 21} Jouke-Jan Hottenga ³⁰ Hilleke E. Hulshoff Pol ³⁵ Kristy S. Hwang ^{95, 96} Clifford R. Jack Jr ⁹⁷ Mark Jenkinson ⁹⁸ Caroline Johnston ^{7, 99} Erik G. Jönsson ^{9, 10} René S. Kahn ^{35, 36} Dalia Kasperaviciute ⁹⁰ Sinead Kelly ^{100, 65} Sungeun Kim ¹⁰¹ Peter M. Kochunov ¹⁰² Laura Koenders ^{31, 30} Bernd Krämer ⁸⁶ John B. J. Kwok ^{103, 104} Jim Lagopoulos ⁹² Gonzalo Laje ¹⁰⁵ Mikael Landén ^{106, 107} Bennett A. Landman ¹⁰⁸ John Lauriello ¹⁰⁹ Stephen M. Lawrie ^{29, 23} Phil H. Lee ^{110, 39} Stephanie Le Hellard ^{19, 55} Hervé Lemaître ^{111, 112, 113, 114} Cassandra D. Leonardo ³³ Chiang-Shan Li ¹¹⁵ Benny Liberg ¹⁰⁷ David C. Liewald ⁶² Xinmin Liu ^{116, 117} Lorna M. Lopez ²³ Eva Loth ⁷ Anbarasu Lourdusamy ¹¹⁸ Michelle Luciano ²³ Fabio Macciardi ^{119, 120} Marise W. J. Machielsen ³¹ Glenda M. MacQueen ^{121, 122} Ulrik F. Malt ^{18, 123} René Mandl ³⁵ Dara S. Manoach ³⁹ Jean-Luc Martinot ^{124, 114, 112, 111} Mar Matarin ⁹⁰ Karen Mather ¹²⁵ Manuel Mattheisen ^{126, 56, 127} Morten Mattingsdal ^{19, 128} Andreas Meyer-Lindenberg ¹²⁹ Colm McDonald ⁴⁸ Andrew McIntosh ^{23, 29} Francis J. McMahon ¹¹⁶ Katie L. McMahon ^{130, 131} Eva Meisenzahl ¹³² Ingrid Melle ^{19, 27} Yuri Milaneschi ^{133, 31, 30} Sebastian Mohnke ⁶⁸ Grant W. Montgomery ¹³⁴ Derek W. Morris ⁶⁵ Eric K. Moses ^{135, 14} Bryon A. Mueller ¹³⁶ Susana Muñoz Maniega ^{23, 24} Thomas W. Mühleisen ^{56, 57} Bertram Müller-Myhsok ^{28, 137} Benson Mwangi ¹³⁸ Matthias Nauck ^{20, 21} Kwangsik Nho ¹³⁹ Thomas E. Nichols ¹⁴⁰ Lars-Göran Nilsson ^{141, 142} Allison C. Nugent ¹¹⁶ Lars Nyberg ^{143, 144} Rene L. Olvera ¹⁴⁵ Jaap Oosterlaan ^{146, 30} Roel A. Ophoff ^{147, 50, 35, 36} Massimo Pandolfo ⁶³ Melina Papalampropoulou-Tsiridou ^{29, 23} Martina Papmeyer ^{23, 29} Tomas Paus ^{148, 149} Zdenka Pausova ¹⁵⁰ Godfrey D. Pearlson ^{20, 115, 21} Brenda W. Penninx ^{31, 30} Charles P. Peterson ¹⁴ Andrea Pfennig ²⁵ Mary Phillips ^{151, 152} G. Bruce Pike ^{148, 122} Jean-Baptiste Poline ^{153, 154} Steven G. Potkin ¹⁵⁵ Benno Pütz ²⁸ Adaikalavan Ramasamy ^{156, 157, 158, 90} Jerod Rasmussen ¹⁵⁵ Marcella Rietschel ^{129, 85} Mark Rijpkema ³⁴ Shannon L. Risacher ^{101, 159} Joshua L. Roffman ⁴⁰ Roberto Roiz-Santiañez ^{60, 61, 160} Nina Romanczuk-Seiferth ⁶⁸ Emma J. Rose ¹⁶¹ Natalie A. Royle ^{162, 24, 23} Dan Rujescu ¹⁶³ Mina Ryten ^{164, 90, 165} Perminder Sachdev ^{166, 103} Alireza Salami ^{143, 144, 167} Theodore D. Satterthwaite ⁸⁸ Jonathan Savitz ^{88, 168, 169} Andrew J. Saykin ⁶⁸ Cathy Scanlon ⁴⁸ Lianne Schmaal ³⁰ Hugo G. Schnack ³⁶ Andrew J. Schork ^{170, 171} S. Charles Schulz ¹⁷² Remmelt Schür ³⁶ Larry Seidman ^{173, 174} Li Shen ¹⁰¹ Jody M. Shoemaker ⁴⁶ Andrew Simmons ^{7, 175, 176} Sanjay Sisodiya ¹⁷⁷ Colin Smith ^{178, 23} Jordan W. Smoller ^{179, 40, 110} Jair C. Soares ¹³⁸ Scott R. Sponheim ^{180, 172} Emma Sprooten ⁷⁸ John M. Starr ^{62, 23, 181} Vidar M. Steen ^{55, 19} Stephen Strakowski ^{182, 183} Lachlan Strike ¹³⁴ Jessika Sussmann ^{29, 23} Philipp G. Sämann ²⁸ Alexander Teumer ²¹ Arthur W. Toga ^{1, 33} Diana Tordesillas-Gutierrez ^{184, 61, 160, 60} Daniah Trabzuni ^{158, 90, 185} Sarah Trost ⁸⁶ Jessica Turner ^{186, 46} Martijn D. van den Heuvel ³⁶ Nic J. van Der Wee ^{187, 188} Kristel van Eijk ^{35, 36} Theo G. M. van Erp ¹⁵⁵ Neeltje E. M. van Haren ³⁶ Dennis van’t Ent ¹⁸⁹ Marie-Jose van Tol ⁹¹ Maria C. Valdés Hernández ²³ Dick J. Veltman ³⁰ Amelia Versace ¹⁵² Henry Völzke ^{190, 20} Robert Walker ¹⁹¹ Henrik Walter ^{68, 192} Lei Wang ¹⁶ Joanna Wardlaw ^{23, 162} Michael E. Weale ¹⁶⁵ Michael W. Weiner ¹⁹³ Wei Wen ¹²⁵ Lars T. Westlye ^{194, 19} Heather C. Whalley ^{29, 195} Christopher D. Whelan ¹² Tonya White ¹⁹⁶ Anderson M. Winkler ^{98, 115} Katharina Wittfeld ⁸³ Girma Woldehawariat ¹¹⁶ Christiane Wolf ²⁸ David Zilles ⁸⁶ Marcel P. Zwiers ³⁴ Anbupalam Thalamuthu ¹²⁵ Peter R. Schofield ^{104, 103} Nelson B. Freimer ^{197, 50} Natalia S. Lawrence ¹⁹⁸ Wayne Drevets ¹⁹⁹

* Corresponding author

1 LONI - Laboratory of Neuro Imaging [Los Angeles]

2 Keck School of Medicine [Los Angeles]

3 David Geffen School of Medicine [Los Angeles]

4 QIMR Berghofer Medical Research Institute

5 Radboud University Medical Center [Nijmegen]

6 Génétique Humaine et Fonctions Cognitives

7 Institute of Psychiatry, Psychology & Neuroscience, King's College London

8 UiO - University of Oslo

9 Department of Clinical Neurosciences, Neurology Division, Karolinska Institutet

10 Karolinska University Hospital [Stockholm]

11 Dalhousie University [Halifax]

12 RCSI - Royal College of Surgeons in Ireland

13 McGill University = Université McGill [Montréal, Canada]

14 Texas Biomedical Research Institute [San Antonio, TX]

15 University of Pittsburgh School of Medicine

16 Northwestern University [Chicago, Ill. USA]

17 University of Iowa [Iowa City]

18 Oslo University Hospital [Oslo]

19 NORMENT - Norwegian Centre for Mental Disorders Research [Oslo]

UiO - University of Oslo, Haukeland University Hospital, Oslo University Hospital [Oslo]

20 Universität Greifswald - University of Greifswald

21 Interfaculty Institute for Genetics and Functional Genomics

22 School of Mathematics and Statistics

23 University of Edinburgh

24 Brain Research Imaging Centre, Imaging Sciences

25 University Hospital Carl Gustav Carus [Dresden, Germany]

26 Semel Institute for Neuroscience and Human Behavior [Los Angeles, Ca]

27 Institute of Clinical Medicine [Oslo]

28 Max Planck Institute of Psychiatry

29 Royal Hospital for Sick Children [Edinburgh]

30 VU University Medical Center [Amsterdam]

31 Department of General Practice/EMGO Institute

32 CCACE - Centre for Cognitive Ageing and Cognitive Epidemiology

33 Keck School of Medicine [Los Angeles]

34 Donders Institute for Brain, Cognition and Behaviour

35 University Medical Center [Utrecht]

36 Brain Centre Rudolf Magnus [Utrecht]

37 Department of Human Genetics [Nijmegen]

38 Psychiatric and Neurodevelopmental Genetics Unit

39 Massachusetts General Hospital [Boston]

40 Department of Psychiatry [Boston]

41 Harvard University [Cambridge]

42 Karakter Child and Adolescent Psychiatry University Centre [Nijmegen]

43 N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia

44 RAS - Russian Academy of Sciences [Moscow]

45 The University of New Mexico [Albuquerque]

46 The Mind Research Network

47 ECE Department - Department of Electrical and Computer Engineering [Albuquerque]

48 NUI Galway - National University of Ireland [Galway]

49 Center for Neurobehavioral Genetics

50 UCLA - University of California [Los Angeles]

51 Institute of Psychological Medicine and Clinical Neurosciences

52 CAMH - Centre for Addiction and Mental Health [Toronto]

53 IBBME - Institute of Biomaterials and Biomedical Engineering [Toronto, ON, Canada]

54 Stanford School of Medicine [Stanford]

55 UiB - University of Bergen

56 University of Bonn

57 Jülich Research Centre

58 Unibas - University of Basel

59 Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada]

60 CIBER-SAM - Centro de Investigación Biomédica en Red Salud Mental [Madrid]

61 IFIMAV - Fundación Marqués de Valdecilla-Instituto de Formación e Investigación Marqués de Valdecilla

62 Centre for Cognitive Ageing and Cognitive Epidemiology

63 ULB - Hôpital Erasme [Bruxelles]

64 School of Psychology, University of Queensland

65 Trinity College Dublin

66 MGH - Department of Psychiatry Massachusetts General Hospital

67 TU Dresden - Technische Universität Dresden = Dresden University of Technology

68 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]

69 Max Planck Institute for Psycholinguistics

70 Department of Medical and Molecular Genetics

71 UTHealth - The University of Texas Health Science Center at Houston

72 South Texas Veterans Health Care System, San Antonio, Texas 78229, USA

73 MSSM - Icahn School of Medicine at Mount Sinai [New York]

74 University Hospital Regensburg

75 NEUROSPIN - Service NEUROSPIN

76 University of Vermont [Burlington]

77 Haukeland University Hospital

78 Dpt of Psychiatry [New Haven]

79 Hartford Hospital

80 University of Oxford [Oxford]

81 Laboratory of Molecular Neuropsychiatry

82 Athinoula A. Martinos Center for Biomedical Imaging

83 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen

84 HELIOS Klinikum Stralsund Hanseatic

85 University of Heidelberg, Medical Faculty

86 Georg-August-University = Georg-August-Universität Göttingen

87 IMPRS - International Max Planck Research School for Language Sciences

88 University of Pennsylvania [Philadelphia]

89 McMaster University [Hamilton, Ontario]

90 UCL, Institute of Neurology [London]

91 UMCG - University Medical Center Groningen [Groningen]

92 Brain and Mind Research Institute

93 Diakonhjemmet Hospital

94 University of Maryland School of Medicine

95 Oakland University

96 University of Rochester School of Medicine

97 Mayo Clinic [Rochester]

98 FMRIB - Oxford Centre for Functional Magnetic Resonance Imaging of the Brain

99 South London and Maudsley NHS Foundation Trust

100 FIMM - Institute for Molecular Medicine Finland [Helsinki]

101 Indiana University School of Medicine

102 University of Maryland [Baltimore]

103 UNSW - University of New South Wales [Sydney]

104 NeuRA - Neuroscience Research Australia

105 UMBC - University of Maryland [Baltimore County]

106 GU - University of Gothenburg

107 Karolinska Institutet [Stockholm]

108 Vanderbilt University [Nashville]

109 Mizzou - University of Missouri [Columbia]

110 BROAD INSTITUTE - Broad Institute of MIT and Harvard

111 UCP - Université de Cergy Pontoise

112 SHFJ - Service Hospitalier Frédéric Joliot

113 U1000 - Neuroimagerie en psychiatrie

114 SCLIN - Clinatec - Centre de recherche biomédicale Edmond J.Safra

115 Department of Neuroscience, Yale University School of Medicine

116 NIH - National Institutes of Health [Bethesda]

117 CUMC - Columbia University Medical Center

118 UON - University of Nottingham, UK

119 UC Irvine - University of California [Irvine]

120 UNIMI - Università degli Studi di Milano = University of Milan

121 Hotchkiss Brain Institute

122 University of Calgary

123 HiOA - Oslo and Akershus University College of Applied Sciences [Oslo]

124 U1000 - Neuroimagerie en psychiatrie

125 Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney

126 Department of Genomics

127 Aarhus University [Aarhus]

128 Sorlandet Hospital HF

129 Medical Faculty [Mannheim]

130 Centre for Advanced Imaging

131 CAI - Centre for Advanced Imaging [Brisbane]

132 LMU - Ludwig Maximilian University [Munich]

133 Translational Gerontology Branch

134 Queensland Institute of Medical Research

135 UWA - The University of Western Australia

136 University of Minnesota [Morris]

137 SyNergy - Munich Cluster for systems neurology [Munich]

138 The University of Texas Medical School at Houston

139 Indiana State University

140 Department of Statistics [Warwick]

141 Stockholm Brain Institute [Stockholm, Sweden]

142 Stockholm University

143 Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå 901 87, Sweden

144 Umeå University

145 University of Texas Health Science Center

146 Department of Clinical Neuropsychology

147 Center for Neurobehavioral Genetics

148 MNI - McConnell Brain Imaging Centre

149 RRI - Rotman Research Institute at the Baycrest Centre

150 SickKids - The Hospital for sick children [Toronto]

151 Department of Psychiatry

152 PITT - University of Pittsburgh

153 PARIETAL - Modelling brain structure, function and variability based on high-field MRI data

NEUROSPIN - Service NEUROSPIN, Inria Saclay - Ile de France

154 UC Berkeley - University of California [Berkeley]

155 Department of Psychiatry and Human Behavior [Irvine]

156 Department of Medical and Molecular Genetics

157 Reta Lila Weston Institute, UCL Institute of Neurology

158 Department of Molecular Neuroscience

159 Indiana Alzheimer Disease Center

160 University of Cantabria, Santander

161 RTI International - Research Triangle Institute International

162 Centre for Cognitive Ageing and Cognitive Epidemiology

163 MLU - Martin-Luther-Universität Halle Wittenberg

164 Department of Medical and Molecular Genetics

165 King‘s College London

166 Prince of Wales Hospital

167 Karolinska Institute

168 Laureate institute for brain research, Tulsa

169 University of Tulsa

170 CogSci - UC San Diego - Department of Cognitive Sciences [Univ California San Diego]

171 UC San Diego - University of California [San Diego]

172 University of Minnesota Medical School

173 BIDMC - Beth Israel Deaconess Medical Center [Boston]

174 HMS - Harvard Medical School [Boston]

175 Maudsley NHS Foundation Trust and Institute of Psychiatry

176 NIHR Biomedical Research Centre [London]

177 Institute of Neurology [London]

178 Edinburgh Dementia Prevention & Centre for Clinical Brain Sciences

179 Center for Human Genetic Research

180 VA NY Harbor Health Care System

181 Alzheimer Scotland Dementia Research Centre

182 Department of Psychiatry and Behavioral Neuroscience [UC, Cincinnati]

183 University of Cincinnati College of Medicine

184 Marqués de Valdecilla University Hospital [Santander]

185 KFSHRC - King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia]

186 Georgia State University

187 Psychiatry and Leiden Institute for Brain and Cognition

188 Leiden University Medical Center (LUMC)

189 Department of Biological Psychology [Amsterdam]

190 Institute for Community Medicine

191 The Centre for Regenerative Medicine

University of Edinburgh

192 Berlin School of Mind and Brain [Berlin]

193 UC San Francisco - University of California [San Francisco]

194 Department of Psychology [Oslo]

195 School of Chemistry, University of Edinburgh

196 Department of Public Health, Erasmus University Medical Centre, Rotterdam

197 Department of Psychiatry and Biobehavioral Sciences

198 University of Exeter

199 Janssen Research & Development

Abstract : The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

Keywords : Genetics MRI GWAS Consortium Meta-analysis Multi-site

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Life Sciences [q-bio] / Neurons and Cognition [q-bio.NC]

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Submitted on : Sunday, December 30, 2018 - 6:06:50 PM
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