Common genetic variants influence human subcortical brain structures. - Archive ouverte HAL Access content directly
Journal Articles Nature Year : 2015

Common genetic variants influence human subcortical brain structures.

Derrek P Hibar (1) , Jason L Stein (1) , Miguel E Renteria (2) , Alejandro Arias-Vasquez (3, 4) , Sylvane Desrivières (5) , Neda Jahanshad (1) , Roberto Toro (6, 7, 8) , Katharina Wittfeld (9, 10) , Lucija Abramovic (11) , Micael Andersson (12) , Benjamin S Aribisala (13, 14) , Nicola J Armstrong (15) , Manon Bernard (16) , Marc M Bohlken (11) , Marco P Boks (11) , Janita Bralten (17, 18) , Andrew A Brown (19) , M Mallar Chakravarty (20) , Qiang Chen (21) , Christopher R K Ching (22) , Gabriel Cuellar-Partida (2) , Anouk den Braber (23) , Sudheer Giddaluru (19, 24) , Aaron L Goldman (25) , Oliver Grimm (26) , Tulio Guadalupe (27, 28) , Johanna Hass (29) , Girma Woldehawariat (30) , Avram J Holmes (31, 32) , Martine Hoogman (33) , Deborah Janowitz (10) , Tianye Jia (34) , Sungeun Kim (35, 36) , Marieke Klein , Bernd Kraemer (37) , Phil H Lee (38) , Loes M Olde Loohuis (39) , Michelle Luciano (40) , Christine Macare (5) , Karen A Mather (41) , Manuel Mattheisen (42, 43, 44) , Yuri Milaneschi (45) , Kwangsik Nho (35, 36) , Martina Papmeyer (13) , Adaikalavan Ramasamy (46) , Shannon L Risacher (35, 36) , Roberto Roiz-Santiañez (47) , Emma J Rose (48) , Alireza Salami (49, 50) , Philipp G Sämann (51) , Lianne Schmaal (45) , Andrew J Schork (52, 53) , Jean Shin (54) , Lachlan T Strike (55, 56, 57) , Alexander Teumer (58) , Marjolein M J van Donkelaar (17, 18) , Kristel R van Eijk (11) , Raymond K Walters (59) , Lars T Westlye (19, 60) , Christopher D Whelan (1) , Anderson M Winkler (61) , Marcel P Zwiers (18) , Saud Alhusaini (62, 63) , Lavinia Athanasiu (19) , Stefan Ehrlich (64) , Marina M H Hakobjan (17, 18) , Cecilie B Hartberg (19, 65) , Unn K Haukvik (19) , Angelien J G a M Heister (17, 18) , David Hoehn (51) , Dalia Kasperaviciute (66, 67) , David C M Liewald (13) , Lorna M Lopez (13) , Remco R R Makkinje (17, 18) , Mar Matarin (68) , Marlies a M Naber (17, 18) , D Reese Mckay (69, 70) , Margaret Needham (71) , Allison C Nugent (72) , Benno Pütz (73) , Natalie A Royle (13) , Li Shen (74) , Emma Sprooten (13, 69, 70) , Daniah Trabzuni (75, 76) , Saskia S L van Der Marel (17, 18) , Kimm J E van Hulzen (17, 18) , Esther Walton (77) , Christiane Wolf (78, 79) , Laura Almasy (80) , David Ames (81) , Sampath Arepalli (82) , Amelia A Assareh (83) , Mark E Bastin (13) , Henry Brodaty (84, 85) , Kazima B Bulayeva (86) , Melanie A Carless (87) , Sven Cichon (42, 43, 88, 89) , Aiden Corvin (90, 91) , Joanne E Curran (92) , Michael Czisch (93) , Greig I de Zubicaray (94) , Allissa Dillman (95) , Ravi Duggirala (87) , Thomas D Dyer (87, 96) , Susanne Erk (97) , Iryna O Fedko (23) , Luigi Ferrucci (30) , Tatiana M Foroud (98) , Peter T Fox (96, 99) , Masaki Fukunaga (100) , J Raphael Gibbs (75, 101) , Harald H H Göring (102) , Robert C Green (103) , Sebastian Guelfi (75) , Narelle K Hansell (40) , Catharina A Hartman (40) , Katrin Hegenscheid (10) , Andreas Heinz (104) , Dena G Hernandez (105) , Dirk J Heslenfeld (10) , Pieter J Hoekstra (106) , Florian Holsboer (107) , Georg Homuth (108) , Jouke-Jan Hottenga (58) , Masashi Ikeda (109) , Clifford R Jack (110) , Mark Jenkinson (111) , Robert Johnson (112) , Ryota Kanai (113, 114) , Maria Keil (37) , Jack W Kent (115) , Peter Kochunov (116) , John B Kwok (117) , Stephen M Lawrie (13) , Xinmin Liu (30, 118) , Dan L Longo (119) , Katie L Mcmahon (120) , Eva Meisenzahl (121) , Ingrid Melle (122, 123, 124, 125) , Sebastian Mohnke (126) , Grant W Montgomery (127, 55) , Jeanette C Mostert (17, 18) , Thomas W Mühleisen (42, 43) , Michael A Nalls (30) , Thomas E Nichols (128) , Lars G Nilsson (49) , Markus M Nöthen (42, 43) , Kazutaka Ohi (129) , Rene L Olvera (130) , Rocio Perez-Iglesias (47, 58) , G Bruce Pike (131, 131) , Steven G Potkin (132) , Ivar Reinvang (60) , Simone Reppermund (84) , Marcella Rietschel (133, 134) , Nina Romanczuk-Seiferth (126) , Glenn D Rosen (135) , Dan Rujescu (136) , Knut Schnell (137) , Peter R Schofield (138) , Colin Smith (139) , Vidar M Steen (19, 24) , Jessika E Sussmann (13) , Anbupalam Thalamuthu (140) , Arthur W Toga (141) , Bryan J Traynor (95) , Juan Troncoso (142) , Jessica A Turner (143) , Maria C Valdés Hernández (13) , Dennis van 'T Ent (23) , Marcel van Der Brug (144) , Nic J A van Der Wee (145) , Marie-Jose van Tol (146) , Dick J Veltman (45) , Thomas H Wassink (147) , Eric Westman (148) , Ronald H Zielke (112) , Alan B Zonderman (30) , David G Ashbrook (149) , Reinmar Hager (149) , Lu Lu (150, 151) , Francis J Mcmahon , Derek W Morris (90, 91) , Robert W Williams (152) , Han G Brunner (153) , Randy L Buckner (154) , Jan K Buitelaar (155) , Wiepke Cahn (156) , Vince D Calhoun (157, 158) , Gianpiero L Cavalleri (159) , Benedicto Crespo-Facorro (47) , Anders M Dale (160) , Gareth E Davies (161) , Norman Delanty (63, 162) , Chantal Depondt (163) , Srdjan Djurovic (122, 164) , Wayne C Drevets (165) , Thomas Espeseth (19, 60) , Randy L Gollub (166) , Beng-Choon Ho (167) , Wolfgang Hoffmann (168) , Norbert Hosten (10) , René S Kahn , Stephanie Le Hellard (19, 24) , Andreas Meyer-Lindenberg (26) , Bertram Müller-Myhsok (169) , Matthias Nauck (170) , Lars Nyberg (171) , Massimo Pandolfo (163) , Brenda W J H Penninx (127) , Joshua L Roffman (32) , Sanjay M Sisodiya (68) , Jordan W Smoller (172, 173) , Hans van Bokhoven (174) , Neeltje E M van Haren (11) , Henry Völzke (175) , Henrik Walter (176) , Michael W Weiner (177) , Wei Wen (178) , Tonya White (179, 180) , Ingrid Agartz (122) , Ole A Andreassen (122, 123) , John Blangero (87, 96) , Dorret I Boomsma (58) , Rachel M Brouwer (181) , Dara M Cannon (165) , Mark R Cookson (182) , Eco J C de Geus (40) , Ian J Deary (183) , Gary Donohoe (90, 165) , Guillén Fernández (184, 185) , Simon E Fisher (18, 27) , Clyde Francks (18, 27) , David C Glahn (69, 70) , Hans J Grabe (186) , Oliver Gruber (187) , John Hardy (75) , Ryota Hashimoto (188) , Hilleke E Hulshoff Pol (11) , Erik G Jönsson (189, 190) , Iwona Kloszewska (191) , Simon Lovestone (192) , Venkata S Mattay (193) , Patrizia Mecocci (194) , Colm Mcdonald (195) , Andrew M Mcintosh (196) , Roel A Ophoff (197) , Tomas Paus (198, 199) , Zdenka Pausova (200) , Mina Ryten (75, 201) , Perminder S Sachdev (41, 178) , Andrew J Saykin (35, 36, 126) , Andy Simmons (202) , Andrew Singleton (82) , Hilkka Soininen (203) , Joanna M Wardlaw (13) , Michael E Weale (204) , Daniel R Weinberger (205, 206) , Hieab H H Adams (207) , Lenore J Launer (18) , Stephan Seiler (208) , Reinhold Schmidt (209) , Ganesh Chauhan (210) , Claudia L Satizabal (211) , James T Becker (212) , Lisa Yanek (213) , Sven J van Der Lee (214) , Maritza Ebling (166, 215) , Bruce Fischl (216, 166) , W T Longstreth (217) , Douglas Greve (166, 215) , Helena Schmidt (218) , Paul Nyquist (219) , Louis N Vinke (166, 215) , Cornelia M van Duijn (220, 221, 214) , Luting Xue (222) , Bernard Mazoyer (223) , Joshua C Bis (217) , Vilmundur Gudnason (224, 225) , Sudha Seshadri (226) , M Arfan Ikram (221, 214) , Nicholas G Martin (227) , Margaret J Wright (2, 228) , Gunter Schumann (5) , Barbara Franke (17, 18) , Paul M Thompson (1) , Sarah E Medland (229, 55)
1 David Geffen School of Medicine [Los Angeles]
2 QIMR Berghofer Medical Research Institute
3 Department of Psychiatry
4 Department of Human Genetics
5 Institute of Psychiatry, Psychology & Neuroscience, King's College London
6 PRES Sorbonne Paris Cité
7 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
8 CNRS - UMR3571 - Gènes, Synapses et Cognition
9 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
10 Greifswald University Hospital
11 University Medical Center [Utrecht]
12 European Commission
13 University of Edinburgh
14 LASU - Lagos State University
15 HWU - Heriot-Watt University [Edinburgh]
16 Unité d'expérimentation sur les Ruminants de Theix
17 Radboud University Medical Center [Nijmegen]
18 Donders Institute for Brain, Cognition and Behaviour
19 UiO - University of Oslo
20 Montreal Neurological Institute and Hospital
21 School of Technical Physics
22 Dept. of Mechanical Engineering
23 Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands
24 Haukeland University Hospital
25 PC2A - Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522
26 Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim
27 Language and Genetics Department [Nijmegen]
28 IMPRS - International Max Planck Research School for Language Sciences
29 Georgia Institute of Technology [Atlanta]
30 NIH - National Institutes of Health [Bethesda, MD, USA]
31 Yale University [New Haven]
32 Department of Psychiatry
33 Mental Health Sciences Unit
34 BNU - Beijing Normal University
35 Indiana University School of Medicine
36 Indiana Alzheimer Disease Center
37 Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany
38 Scottish Fish Immunology Research Centre, School of Biological Sciences
39 UCLA - University of California [Los Angeles]
40 Medstar Research Institute
41 Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia
42 Department of Genomics, Life and Brain Center
43 Institute of Human Genetics
44 Department of Biomedicine and the Centre for Integrative Sequencing
45 Department of Psychiatry
46 Respiratory Epidemiology and Public Health
47 CIBER-SAM - Centro de Investigación Biomédica en Red Salud Mental [Madrid]
48 IPCM - Institut Parisien de Chimie Moléculaire
49 Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå 901 87, Sweden
50 ARC - Aging Research Center [Karolinska Institutet]
51 Max Planck Institute of Psychiatry
52 Neuro - UC San Diego - Department of Neurosciences [Univ California San Diego]
53 CogSci - UC San Diego - Department of Cognitive Sciences [Univ California San Diego]
54 SickKids - The Hospital for sick children [Toronto]
55 Queensland Institute of Medical Research
56 School of Psychology, University of Queensland, Brisbane 4072, Australia
57 Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia
58 King‘s College London
59 Department of Genomics of Common Disease
60 Department of Psychology [Oslo]
61 Deutsche Bundesbank
62 Department of Neurology and Neurosurgery [Montreal]
63 Molecular and Cellular Therapeutics
64 MetaGenoPolis
65 Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway
66 UCL Institute of Neurology and Epilepsy Society
67 Department of Medicine
68 Clinical And Experimental Epilepsy
69 Dpt of Psychiatry [New Haven]
70 Hartford Hospital
71 Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland
72 Institute of Food & Health, University College Dublin,
73 Statistical Genetics Group
74 State Key Laboratory of Lead Compound Research
75 Reta Lila Weston Institute of Neurological Studies
76 Department of Genetics
77 EDC - Centre épigénétique et destin cellulaire
78 Dundee Technopole
79 Ninewells Hospital and Medical School, Biomedical Research Centre
80 Department of Genetics
81 Department of Psychiatry and National Ageing Research Institute
82 Department of Clinical Genetics
83 Department of Medical Parasitology and Mycology
84 Centre for Healthy Brain Ageing
85 Dementia Collaborative Research Centre
86 N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia
87 Texas Biomedical Research Institute [San Antonio, TX]
88 INM-1 - Institute of Neuroscience and Medicine
89 Division of Medical Genetics
90 Department of Psychiatry
91 Neuropsychiatric Genetics Research Group
92 Department of Materials Science & Metallurgy
93 Bijvoet Center of Biomolecular Research [Utrecht]
94 School of Psychology, University of Queensland
95 Laboratory of Neurogenetics
96 UTHealth - The University of Texas Health Science Center at Houston
97 Department of Genomics
98 Department of Medical and Molecular Genetics
99 South Texas Veterans Health Care System, San Antonio, Texas 78229, USA
100 Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
101 University of Melbourne
102 Public Health Genomics Unit
103 Department of Biomolecular Engineering
104 Rheinische Friedrich-Wilhelms-Universität Bonn
105 Estación Experimental de Pastos y Forrajes “Indio Hatuey”
106 Department of Psychiatry
107 Neuronal Plasticity / Mouse Behaviour
108 Interfaculty Institute for Genetics and Functional Genomics
109 Department of Psychiatry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
110 Department of Radiology
111 Department of Clinical Neurology [Oxford]
112 University of Maryland School of Medicine
113 University of Sussex
114 Institute of Cognitive Neuroscience
115 United Kingdom Met Office [Exeter]
116 Department of Psychiatry
117 Department of Civil and Structural Engineering
118 CUIMC - Columbia University Irving Medical Center
119 Lymphocyte Cell Biology Unit, Laboratory of Genetics
120 Centre for Advanced Imaging
121 Psychiatry and Psychotherapy
122 KG Jebsen Centre for Psychosis Research
123 Division of Mental Health and Addiction
124 Institute of Clinical Medicine [Oslo]
125 Division of Mental Health and Addiction
126 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
127 Genetic Epidemiology Unit
128 Department of Statistics [Warwick]
129 Department of Psychiatry
130 Department of Medical and Molecular Genetics
131 University of Calgary
132 Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA
133 Department of Genetic Epidemiology in Psychiatry
134 Department of Psychiatry
135 Space and Naval Warfare Systems Center
136 Klinik für Psychiatrie
137 Department of Psychiatry, Division of Medical Psychology
138 Genetics of Mental Illness and Brain Function
139 UMR DAP - Développement et amélioration des plantes
140 Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia
141 LONI - Laboratory of Neuro Imaging [Los Angeles]
142 Departamento de Física Aplicada
143 Georgia State University
144 Genentech, Inc. [San Francisco]
145 Psychiatry and Leiden Institute for Brain and Cognition
146 LUMC - Leiden University Medical Center
147 Department of Psychiatry
148 Department of Neurobiology, Care Sciences and Society
149 University of Manchester [Manchester]
150 UTHSC - The University of Tennessee Health Science Center [Memphis]
151 iangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China
152 CUDOS - Centre for Ultrahigh Bandwidth Devices for Optical Systems
153 Department of Human Genetics
154 Cognitive Neuroscience Laboratory (CNL)
155 Donders Center for Cognitive Neuroimaging
156 Department of Psychiatry
157 The Mind Research Network
158 ECE Department - Department of Electrical and Computer Engineering [Albuquerque]
159 Division of Molecular and Cellular Therapeutics
160 SAMS - Scottish Association for Marine Science
161 Structural Biology Laboratory, Department of Chemistry, University of York
162 Neurology Division, Beaumont Hospital, Dublin 9, Ireland
163 Department of Neurology
164 Deparment of Medical Genetics
165 Human Genetics Branch
166 Athinoula A. Martinos Center for Biomedical Imaging
167 Department of Psychiatry, University of Iowa
168 Institute for Community Medicine, Department Epidemiology of Health Care and Community Health
169 Translational Centre for Regenerative Medicine (TRM); Department of Cell Therapy
170 Institute of Clinical Chemistry and Laboratory Medicine
171 Department of Health Science, Division of Health and Rehabilitation
172 Stanley Center for Psychiatric Research
173 Psychiatric and Neurodevelopmental Genetics Unit
174 849 Department of Human Genetics
175 Institute for Community Medicine
176 Institute for Energy Systems and Thermodynamics
177 Renyi Institute
178 Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW
179 Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam 3000 CB, The Netherlands
180 Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands
181 VU - Vrije Universiteit Amsterdam [Amsterdam]
182 Cell Biology and Gene Expression Section
183 Dept of Psychology
184 Laboratoire de Recherche Magellan
185 ISEOR - Institut de Socio-économie des Entreprises et des ORganisations
186 Department of Psychiatry and Psychotherapy
187 LIG - Laboratoire d'Informatique de Grenoble
188 Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development,
189 Centre for Allergy Research
190 Department of Medicine, Clinical Pharmacology Unit
191 MUL - Medical University of Łódź
192 Psychiatry Institute
193 Department of Health and Human Services
194 Institute of Gerontology and Geriatrics
195 CSIRO - Commonwealth Scientific and Industrial Research Organisation [Canberra]
196 Australian Centre for Research into Injury in Sport and its Prevention
197 Department of Psychiatry
198 School of Psychology [Nottingham]
199 MNI - McConnell Brain Imaging Centre
200 SickKids - The Hospital for sick children
201 Department of Medical and Molecular Genetics
202 ECMWF - European Centre for Medium-Range Weather Forecasts
203 University of Eastern Finland
204 Centre for Population Health Sciences
205 LIBD - Lieber Institute for Brain Development [Baltimore]
206 JHU - Johns Hopkins University
207 Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique
208 Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria
209 AIT - Austrian Institute of Technology [Vienna]
210 INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France
211 INSERM, Neuroepidemiology U708, Bordeaux, France
212 KIT - Karlsruhe Institute of Technology
213 General Internal Medicine, Johns Hopkins School of Medicine
214 Erasmus MC - Erasmus University Medical Center [Rotterdam]
215 HMS - Harvard Medical School [Boston]
216 CSAIL - Computer Science and Artificial Intelligence Laboratory [Cambridge]
217 University of Washington [Seattle]
218 Department of Physics [Stockholm]
219 Department of Neurology
220 Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands
221 Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands
222 BU - Boston University [Boston]
223 GIN - UMR 5296 - Groupe d'Imagerie Neurofonctionnelle
224 Faculty of Medicine
225 Icelandic Heart Association, Kopavogur, Iceland.
226 BUSM - Boston University School of Medicine
227 LIMATB - Laboratoire d'Ingénierie des Matériaux de Bretagne
228 School of Psychology, University of Queensland, Brisbane 4072, Australia
229 BROAD INSTITUTE - Broad Institute of MIT and Harvard
Marieke Klein
  • Function : Author
Stefan Ehrlich
  • Function : Author
Unn K Haukvik
  • Function : Author
Laura Almasy
Francis J Mcmahon
  • Function : Author
René S Kahn
  • Function : Author
Michael W Weiner
  • Function : Author
Ian J Deary
  • Function : Author
Hilkka Soininen
Bernard Mazoyer

Abstract

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Domains

Neuroscience

Dates and versions

hal-01196805 , version 1 (11-09-2015)

Identifiers

Cite

Derrek P Hibar, Jason L Stein, Miguel E Renteria, Alejandro Arias-Vasquez, Sylvane Desrivières, et al.. Common genetic variants influence human subcortical brain structures.. Nature, 2015, 520 (7546), pp.224-9. ⟨10.1038/nature14101⟩. ⟨hal-01196805⟩
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