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Nat Commun. 2017 Jan 18;8:13624. doi: 10.1038/ncomms13624.

Novel genetic loci associated with hippocampal volume.

Hibar DP1, Adams HH2,3, Jahanshad N1, Chauhan G4, Stein JL1,5, Hofer E6,7, Renteria ME8, Bis JC9, Arias-Vasquez A10,11,12,13, Ikram MK2,14,15,16,17, Desrivières S18, Vernooij MW2,3, Abramovic L19, Alhusaini S20,21, Amin N2, Andersson M22, Arfanakis K23,24,25, Aribisala BS26,27,28, Armstrong NJ29,30, Athanasiu L31,32, Axelsson T33, Beecham AH34,35, Beiser A36,37,38, Bernard M39, Blanton SH34,35, Bohlken MM19, Boks MP19, Bralten J10,13, Brickman AM40, Carmichael O41, Chakravarty MM42,43, Chen Q44, Ching CR1,45, Chouraki V36,38,46, Cuellar-Partida G8, Crivello F47, Den Braber A48, Doan NT31, Ehrlich S49,50,51, Giddaluru S52,53, Goldman AL44, Gottesman RF54, Grimm O55, Griswold ME56, Guadalupe T57,58, Gutman BA1, Hass J59, Haukvik UK31,60, Hoehn D61, Holmes AJ50,62, Hoogman M10,13, Janowitz D63, Jia T18, Jørgensen KN31,60, Karbalai N61, Kasperaviciute D64,65, Kim S66,67,68, Klein M10,13, Kraemer B69, Lee PH50,70,71,72,73, Liewald DC74, Lopez LM74, Luciano M74, Macare C18, Marquand AF13,75, 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Author information

1
Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging &Informatics Institute, Keck School of Medicine of University of Southern California, Los Angeles, California 90292, USA.
2
Department of Epidemiology, Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands.
3
Department of Radiology and Nuclear Medicine, Erasmus MC, 3015 CE Rotterdam, The Netherlands.
4
INSERM Unit U1219, University of Bordeaux, 33076 Bordeaux, France.
5
Department of Genetics &UNC Neuroscience Center, University of North Carolina (UNC), Chapel Hill, North Carolina, 27599, USA.
6
Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Auenbruggerplatz 22, 8036 Graz, Austria.
7
Institute of Medical Informatics, Statistics and Documentation, Medical University Graz, Auenbruggerplatz 22, 8036 Graz, Austria.
8
QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
9
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, 1730 Minor Avenue/Suite 1360. Seattle, Washington 98101, USA.
10
Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
11
Department of Psychiatry, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
12
Department of Cognitive Neuroscience, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
13
Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 GA Nijmegen, The Netherlands.
14
Academic Medicine Research Institute, Duke-NUS Graduate Medical School, Singapore, 169857, Singapore.
15
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 168751, Singapore.
16
Memory Aging &Cognition Centre (MACC), National University Health System, Singapore, 119228, Singapore.
17
Department of Pharmacology, National University of Singapore, Singapore, 119077, Singapore.
18
MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
19
Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, 3584 CX Utrecht, The Netherlands.
20
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.
21
The Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
22
Department of Integrative Medical Biology and Umeå Center for Functional Brain Imaging, Umeå University, 901 87 Umeå, Sweden.
23
Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois 60616, USA.
24
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois 60612, USA.
25
Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, Illinois 60616, USA.
26
Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK.
27
Department of Computer Science, Lagos State University, Lagos, P.M.B. 01 LASU, Nigeria.
28
Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK.
29
Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, New South Wales 2052, Australia.
30
Mathematics and Statistics, Murdoch University, Perth, Western Australia, 6150, Australia.
31
NORMENT-KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, 0315 Oslo, Norway.
32
NORMENT-KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, 0424 Oslo, Norway.
33
Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Box 1432, SE-751 44 Uppsala, Sweden.
34
Dr John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, Florida, 33136, USA.
35
John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, 33136, USA.
36
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts,02118, USA.
37
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118 USA.
38
Framingham Heart Study, 17 Mount Wayte Avenue, Framingham, Massachusetts 01703 USA.
39
Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8.
40
Taub Institute for Research on Alzheimer's Disease and the Aging Brain; G.H. Sergievsky Center; Department of Neurology. Columbia University Medical Center, 639 West 1168th Street, New York, New York 10032, USA.
41
Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.
42
Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec, Canada H4H 1R3.
43
Department of Psychiatry and Biomedical Engineering, McGill University, Montreal, Quebec, Canada H3A 2B4.
44
Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA.
45
Interdepartmental Neuroscience Graduate Program, UCLA School of Medicine, Los Angeles, California 90095, USA.
46
Lille University, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Risk factors and molecular determinants of aging-related diseases, F-59000 Lille, France.
47
IMN UMR5293, GIN, CNRS, CEA, University of Bordeaux, 146 rue Léo Saignat, 33076 Bordeaux, France.
48
Biological Psychology, Amsterdam Neuroscience, Vrije Universiteit &Vrije Universiteit Medical Center, 1081 BT Amsterdam, The Netherlands.
49
Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, 01307 Dresden, Germany.
50
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
51
Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
52
NORMENT-KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway.
53
Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
54
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
55
Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, 68159 Mannheim, Germany.
56
Department of Data Science, University of Mississippi Medical Center, Jackson, Mississippi, 39216, USA.
57
Language and Genetics Department, Max Planck Institute for Psycholinguistics, 6525 XD Nijmegen, The Netherlands.
58
International Max Planck Research School for Language Sciences, 6525 XD Nijmegen, The Netherlands.
59
Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, 01307 Dresden, Germany.
60
Department of Research and Development, Diakonhjemmet Hospital, 0319 Oslo, Norway.
61
Max Planck Institute of Psychiatry, 80804 Munich, Germany.
62
Department of Psychology, Yale University, New Haven, Connecticut 06520, USA.
63
Department of Psychiatry, University Medicine Greifswald, 17489 Greifswald, Germany.
64
UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, Bucks, SL9 0RJ, UK.
65
Department of Medicine, Imperial College London, London SW7 2AZ, UK.
66
Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
67
Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
68
Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
69
Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, 69120, Germany.
70
Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
71
Harvard Medical School, Boston, Massachusetts 02115, USA.
72
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts 02141, USA.
73
Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, Lexington, Massachusetts, 02421, USA.
74
Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
75
Donders Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, 6525 EN, The Netherlands.
76
Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK.
77
Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark.
78
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, DK-8000 Aarhus and Copenhagen, Denmark.
79
Center for integrated Sequencing, iSEQ, Aarhus University, DK-8000 Aarhus, Denmark.
80
Department of Psychiatry, Yale University, New Haven, Connecticut 06511, USA.
81
Olin Neuropsychiatric Research Center, Hartford, Connecticut 06114, USA.
82
Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, 1081 HL Amsterdam, The Netherlands.
83
Human Genetics Branch, National Institute of Mental Health Intramural Research Program, 35 Convent Drive, Rm 1A202, Bethesda, Maryland 20892-3719, USA.
84
Department of Neurology, Department of Anesthesia/Critical Care Medicine, Department of Neurosurgery, Johns Hopkins, USA600 N. Wolfe St, Baltimore, Maryland 21287, USA.
85
Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA.
86
Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, 1081 HV, The Netherlands.
87
Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK.
88
Division of Systems Neuroscience of Psychopathology, Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, 3060, Switzerland.
89
Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK.
90
The Jenner Institute Laboratories, University of Oxford, Oxford OX3 7DQ, UK.
91
Karakter Child and Adolescent Psychiatry University Center, Nijmegen, 6525 GC, The Netherlands.
92
Department of Medicine and Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, 39008 Santander, Spain.
93
CIBERSAM (Centro Investigación Biomédica en Red Salud Mental), Santander, 39011, Spain.
94
Psychosis Research Group, Department of Psychiatry &Trinity Translational Medicine Institute, Trinity College, Dublin, Dublin 2, Ireland.
95
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK.
96
Department of Neurology, University of Miami, Miller School of Medicine, Miami, Florida, 33136, USA.
97
Department of Epidemiology and Public Health Sciences, University of Miami, Miller School of Medicine, Miami, Florida, 33136, USA.
98
Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, Victoria, 3502, Australia.
99
Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, 3502, Australia.
100
Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
101
Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, California 92093, USA.
102
Department of Cognitive Sciences, University of California, San Diego, California 92161, USA.
103
Icelandic Heart Association, Kopavogur, 201, Iceland.
104
Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.
105
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA.
106
Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4072, Australia.
107
Institute for Community Medicine, University Medicine Greifswald, 17489 Greifswald, Germany.
108
Neuroimaging Unit, Technological Facilities. Valdecilla Biomedical Research Institute IDIVAL, Santander, Cantabria, 39011, Spain.
109
Institut Pasteur, 75015 Paris, France.
110
Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
111
Department of Cardiology, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
112
GeneSTAR Research Center, Department of Medicine, Johns Hopkins University School of Medicine, 1830 E Monument St Suite 8028, Baltimore, Maryland 21287, USA.
113
Department of Radiology, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
114
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, 9700RB, The Netherlands.
115
Brain Center Rudolf Magnus, Human Neurogenetics Unit, UMC Utrecht, 3584 CG Utrecht, The Netherlands.
116
Department of Psychiatry and Human Behavior, University of California-Irvine, Irvine, California 92617, USA.
117
Department of Psychology, Georgia State University, Atlanta, Georgia 30302, USA.
118
NORMENT-KG Jebsen Centre, Department of Psychology, University of Oslo, 0317 Oslo, Norway.
119
Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, 39216, USA.
120
FMRIB Centre, University of Oxford, Oxford OX3 9DU, UK.
121
German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, 17487 Greifswald, Germany.
122
University of Wuerzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, Wuerzburg, 97080, Germany.
123
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA.
124
Biospective Inc, Montreal, Quebec, Canada, 6100 Avenue Royalmount, Montréal, Québec, Canada H4P 2R2.
125
Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
126
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville/Edinburg/San Antonio, Texas, 78250, USA.
127
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
128
Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 29104, USA.
129
National Ageing Research Institute, Royal Melbourne Hospital, Melbourne, Victoria 3052, Australia.
130
Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne, Victoria 3101, Australia.
131
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
132
Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh, 3501 Forbes Ave., Suite 830, Pittsburgh, Pennsylvania 15213, USA.
133
Dementia Collaborative Research Centre-Assessment and Better Care, University of New South Wales, Sydney, New South Wales 2052, Australia.
134
Department of Clinical Genetics and GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.
135
Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.
136
Department of Evolution and Genetics, Dagestan State University, Makhachkala 367000, Dagestan, Russia.
137
The Mind Research Network &LBERI, Albuquerque, New Mexico 87106, USA.
138
Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA.
139
Centre for Neuroimaging &Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, H91 TK33 Galway, Ireland.
140
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119077, Singapore.
141
Division of Medical Genetics, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
142
Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany.
143
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, 52425 Jülich, Germany.
144
Center for Multimodal Imaging and Genetics, University of California, San Diego, California 92093, USA.
145
Departments of Neurosciences, Radiology, Psychiatry, and Cognitive Science, University of California, San Diego, California 92093, USA.
146
Avera Institute for Human Genetics, Sioux Falls, South Dakota 57108, USA.
147
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
148
Program in Translational NeuroPsychiatric Genomics, Departments of Neurology &Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
149
Harvard Medical School, Boston, Massachusetts, 02115, USA.
150
Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, 02142, USA.
151
Broad Institute, Cambridge, Massachusetts, 02142, USA.
152
Faculty of Health and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Queensland 4059, Australia.
153
Department of Neurology, Bordeaux University Hospital, Bordeaux, 33076, France.
154
Imaging of Dementia and Aging (IDeA) Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis, 4860 Y Street, Suite 3700, Sacramento, California 95817, USA.
155
Neurology Division, Beaumont Hospital, Dublin 9, Ireland.
156
Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, 1070 Brussels, Belgium.
157
Department of Medical Genetics, Oslo University Hospital, 0420 Oslo, Norway.
158
Cognitive Genetics and Cognitive Therapy Group, Neuroimaging, Cognition &Genomics Centre (NICOG) &NCBES Galway Neuroscience Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, H91 TK33, Galway, Ireland.
159
Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 8, Ireland.
160
Janssen Research &Development, LLC, Titusville, New Jersey 08560, USA.
161
Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Department of Psychiatry and Psychotherapy, Charitéplatz 1, 10117 Berlin, Germany.
162
Intramural Research Program of the National Institute on Aging, Baltimore, Maryland, 21224, USA.
163
Department of Neurological Sciences &Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois 60616, USA.
164
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, G41 4DQ, UK.
165
Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, 77030, USA.
166
Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
167
University of Texas Health Science Center, San Antonio, Texas 78229, USA.
168
Division of Cerebral Integration, National Institute for Physiological Sciences, Aichi, 444-8585, Japan.
169
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
170
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, 7491, Norway.
171
Department of Radiology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, 7030, Norway.
172
Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
173
Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, 565-0871, Japan.
174
Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, 17489 Greifswald, Germany.
175
German Center for Neurodegenerative Diseases (DZNE), Tübingen, 72076, Germany.
176
Department of Psychology, VU University Amsterdam, 1081 BT Amsterdam, The Netherlands.
177
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115 USA.
178
Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242, USA.
179
HMNC Brain Health, Munich, 80539, Germany.
180
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17489 Greifswald, Germany.
181
Translational Genomics Research Institute, Neurogenomics Division, 445N Fifth Street, Phoenix, Arizona 85004, USA.
182
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan.
183
Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905, USA.
184
NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland 21201, USA.
185
School of Psychology, University of Sussex, Brighton BN1 9QH, UK.
186
Institute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK.
187
Department of Neuroinformatics, Araya Brain Imaging, Tokyo, 102-0093, Japan.
188
Medical University of Lodz, 90-419 Lodz, Poland.
189
Department of Neurology, Mayo Clinic, Rochester, Minnesota, 55905, USA.
190
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, 21228, USA.
191
Neuroscience Research Australia, Sydney, New South Wales 2031, Australia.
192
School of Medical Sciences, UNSW, Sydney, New South Wales 2052, Australia.
193
INSERM UMR 1000 "Neuroimaging and Psychiatry", Service Hospitalier Frédéric Joliot; University Paris-Sud, Université Paris-Saclay, University Paris Descartes, Maison de Solenn, Paris, 91400, France.
194
Columbia University Medical Center, New York, New York 10032, USA.
195
Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
196
Departments of Neurology and Psychiatry, University of Pittsburgh, 3501 Forbes Ave., Suite 830, Pittsburgh Pennsylvania 15213, USA.
197
Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK.
198
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
199
Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland 4072, Australia.
200
Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, 06132 Perugia, Italy.
201
Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.
202
University of Liverpool, Institute of Translational Medicine, Liverpool L69 3BX, UK.
203
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17489 Greifswald, Germany.
204
German Center for Cardiovascular Research (DZHK e.V.), partner site Greifswald, Greifswald, 17475, Germany.
205
Department of Statistics &WMG, University of Warwick, Coventry CV4 7AL, UK.
206
Department of Medical Informatics Erasmus MC, 3015 CE Rotterdam, The Netherlands.
207
Faculty of Applied Sciences, Delft University of Technology, Delft, 2628 CD, The Netherlands.
208
Department of Genomics, Life &Brain Center, University of Bonn, 53127 Bonn, Germany.
209
Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada M6A 2E1.
210
Departments of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8.
211
Child Mind Institute, New York, New York, 10022, USA.
212
Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada M5S 3E2.
213
Department of Radiology, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
214
Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
215
Departments of Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA, USA Group Health Research Institute, Group Health, 1730 Minor Avenue/Suite 1360, Seattle, Washington 98101, USA.
216
Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, New South Wales 2052, Australia.
217
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Pediatrics at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
218
Evelyn F. McKnight Brain Institute, University of Miami, Miller School of Medicine, Miami, Florida, 33136, USA.
219
Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia.
220
Institute of Molecular Biology and Biochemistry, Medical University Graz, Harrachgasse 21/III, 8010 Graz, Austria.
221
Department of Neuroimaging, Institute of Psychiatry, King's College London, London SE5 8AF, UK.
222
Biomedical Research Centre for Mental Health, King's College London, London SE5 8AF, UK.
223
Biomedical Research Unit for Dementia, King's College London, London SE5 8AF, UK.
224
MRC Edinburgh Brain Bank, University of Edinburgh, Academic Department of Neuropathology, Centre for Clinical Brain Sciences, Edinburgh, EH16 4SB UK.
225
Institute of Clinical Medicine, Neurology, University of Eastern Finland, FI-70211 Kuopio, Finland.
226
Neurocentre Neurology, Kuopio University Hospital, FI-70211 Kuopio, Finland.
227
Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, G4 0SF, UK.
228
Laboratory of Neuro Imaging, Institute for Neuroimaging and Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA.
229
Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21205, USA.
230
3rd Department of Neurology, "G. Papanicolaou", Hospital, Aristotle University of Thessaloniki, Thessaloniki, 57010, Greece.
231
Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR1219, Bordeaux, F-33000, France.
232
Department of Internal Medicine, Erasmus MC, 3015 CE Rotterdam, The Netherlands.
233
Genentech Inc., South San Francisco, California 94080, USA.
234
Department of Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
235
University of Groningen, University Medical Center Groningen, Department of Neuroscience, 9713 AW Groningen, the Netherlands.
236
Department of Internal Medicine and Geriatric Medicine, INSERM U1027, University of Toulouse, Toulouse, 31024, France.
237
Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
238
Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
239
Center for Imaging of Neurodegenerative Disease, San Francisco VA Medical Center, University of California, San Francisco, California 94121, USA.
240
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, SE-141 57 Huddinge, Sweden.
241
Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia Children's Hospital, 3015 CE Rotterdam, The Netherlands.
242
Laboratory of Epidemiology &Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
243
Departments of Neurology and Epidemiology, University of Washington, 325 Ninth Avenue, Seattle, Washington 98104-2420, USA.
244
Intramural Research Program, NIA, NIH, 7201 Wisconsin Ave, Suite 3C-309, Bethesda, Maryland 20892, USA.

Abstract

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

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