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Nat Neurosci. 2016 Dec;19(12):1569-1582. doi: 10.1038/nn.4398. Epub 2016 Oct 3.

Novel genetic loci underlying human intracranial volume identified through genome-wide association.

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Author information

1
Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
2
Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands.
3
Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.
4
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
5
Lille University, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE - Risk factors and molecular determinants of aging-related diseases, Lille, France.
6
Framingham Heart Study, Framingham, Massachusetts, USA.
7
Department of Genetics and UNC Neuroscience Center, University of North Carolina (UNC), Chapel Hill, North Carolina, USA.
8
Department of Neurology, Department of Anesthesia/Critical Care Medicine, Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland, USA.
9
QIMR Berghofer Medical Research Institute, Brisbane, Australia.
10
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
11
Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
12
Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands.
13
Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands.
14
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.
15
MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
16
Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, Florida, USA.
17
John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.
18
German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald, Germany.
19
Department of Psychiatry, University Medicine Greifswald, Greifswald, Germany.
20
Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht, the Netherlands.
21
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
22
The Royal College of Surgeons in Ireland, Dublin 2, Ireland.
23
Department of Integrative Medical Biology and Umeå center for Functional Brain Imaging, Umeå University, Umeå, Sweden.
24
Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, USA.
25
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
26
Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, Illinois, USA.
27
Brain Research Imaging Centre, University of Edinburgh, Edinburgh, UK.
28
Department of Computer Science, Lagos State University, Lagos, Nigeria.
29
Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh, UK.
30
Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
31
Mathematics and Statistics, Murdoch University, Perth, Australia.
32
NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
33
NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
34
Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
35
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
36
Hospital for Sick Children, University of Toronto, Toronto, Canada.
37
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
38
Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands.
39
Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
40
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.
41
G.H. Sergievsky Center, Columbia University Medical Center, New York, New York, USA.
42
Department of Neurology, Columbia University Medical Center, New York, New York, USA.
43
Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
44
Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada.
45
Department of Psychiatry and Biomedical Engineering, McGill University, Montreal, Canada.
46
INSERM Unit U1219, University of Bordeaux, France.
47
Lieber Institute for Brain Development, Baltimore, Maryland, USA.
48
Interdepartmental Neuroscience Graduate Program, UCLA School of Medicine, Los Angeles, California, USA.
49
Biological Psychology, Neuroscience Campus Amsterdam, Vrije Universiteit University and Vrije Universiteit Medical Center, Amsterdam, the Netherlands.
50
Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Germany.
51
Department of Psychiatry, Massachusetts General Hospital, Boston, Masschusetts, USA.
52
Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, North Carolina, USA.
53
NSERM Unit 1000 ″Neuroimaging and Psychiatry″, University Paris Sud, University Paris Descartes, Paris, France.
54
Maison de Solenn, Adolescent Psychopathology and Medicine Department, APHP Hospital Cochin, Paris, France.
55
Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
56
Harvard Medical School, Boston, Massachusetts, USA.
57
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts, USA.
58
NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Norway.
59
Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
60
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
61
Karakter Child and Adolescent Psychiatry University Center, Nijmegen, the Netherlands.
62
King's College London, Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychology, Psychiatry and Neurosciene, London, UK.
63
Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.
64
Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
65
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
66
International Max Planck Research School for Language Sciences, Nijmegen, the Netherlands.
67
Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden, Germany.
68
Department of Research and Development, Diakonhjemmet Hospital, Oslo, Norway.
69
Department of Pharmacology, National University of Singapore, Singapore.
70
Memory Aging and Cognition Centre (MACC), National University Health System, Singapore.
71
Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Austria, Graz, Austria.
72
Institute of Medical Informatics, Statistics and Documentation, Medical University Graz, Austria, Graz, Austria.
73
Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, Germany.
74
Department of Psychology, Yale University, New Haven, Connecticut, USA.
75
UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, Bucks, UK.
76
Department of Medicine, Imperial College London, London, UK.
77
Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA.
78
Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
79
Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
80
Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany.
81
Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, Lexington, Massachusetts, USA.
82
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
83
Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh, UK.
84
Donders Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, The Netherlands.
85
Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
86
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
87
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark.
88
Center for integrated Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
89
UMR5296 University of Bordeaux, CNRS, CEA, Bordeaux, France.
90
Department of Psychiatry, Yale University, New Haven, Connecticut, USA.
91
Olin Neuropsychiatric Research Center, Hartford, Connecticut, USA.
92
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
93
Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
94
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland, USA.
95
Center for Neurobehavioral Genetics, University of California, Los Angeles, California, USA.
96
Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, the Netherlands.
97
Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK.
98
Division of Systems Neuroscience of Psychopathology, Translational Research Center, University Hospital of Psychiatry, University of Bern, Switzerland.
99
School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, Rotterdam, the Netherlands.
100
Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, Illinois, USA.
101
Department of Medical and Molecular Genetics, King's College London, London, UK.
102
The Jenner Institute Laboratories, University of Oxford, Oxford, UK.
103
Department of Medicine and Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander, Spain.
104
CIBERSAM (Centro Investigación Biomédica en Red Salud Mental), Santander, Spain.
105
Psychosis Research Group, Department of Psychiatry and Trinity Translational Medicine Institute, Trinity College Dublin.
106
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
107
Department of Neurology, University of Miami, Miller School of Medicine, Miami, Florida, USA.
108
Department of Epidemiology and Public Health Sciences, University of Miami, Miller School of Medicine, Miami, Florida, USA.
109
Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia.
110
Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
111
Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
112
Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, USA.
113
Department of Cognitive Sciences, University of California, San Diego, USA.
114
Icelandic Heart Association, Kopavogur, Iceland.
115
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
116
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
117
Queensland Brain Institute, University of Queensland, Brisbane, Australia.
118
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
119
School of Computing Engineering and Mathematics, Western Sydney University, Parramatta, Australia.
120
Neuroimaging Unit,Technological Facilities. Valdecilla Biomedical Research Institute IDIVAL, Santander, Cantabria, Spain.
121
Institut Pasteur, Paris, France.
122
Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
123
GeneSTAR Research Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
124
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
125
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
126
Brain Center Rudolf Magnus, Human Neurogenetics Unit, UMC Utrecht, Utrecht, the Netherlands.
127
Department of Psychiatry and Human Behavior, University of California-Irvine, Irvine, California, USA.
128
NORMENT - KG Jebsen Centre, Department of Psychology, University of Oslo, Oslo, Norway.
129
Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
130
FMRIB Centre, University of Oxford, Oxford, UK.
131
University of Wuerzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, Wuerzburg, Germany.
132
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
133
Biospective Inc, Montreal, Quebec, Canada, Montréal, Québec, Canada.
134
Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
135
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine Brownsville/Edinburg/San Antonio, Texas, USA.
136
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
137
Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
138
National Ageing Research Institute, Royal Melbourne Hospital, Melbourne, Australia.
139
Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne, Australia.
140
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
141
Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
142
Dementia Collaborative Research Centre - Assessment and Better Care, UNSW, Sydney, Australia.
143
Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands.
144
Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.
145
Department of Evolution and Genetics, Dagestan State University, Makhachkala, Dagestan, Russia.
146
The Mind Research Network and LBERI, Albuquerque, New Mexico, USA.
147
Department of ECE, University of New Mexico, Albuquerque, New Mexico, USA.
148
Centre for Neuroimaging and Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
149
Academic Medicine Research Institute, Duke-NUS Graduate Medical School, Singapore.
150
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
151
Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland.
152
Institute of Human Genetics, University of Bonn, Bonn, Germany.
153
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
154
Center for Multimodal Imaging and Genetics, University of California, San Diego, California, USA.
155
Department of Neurosciences, University of California, San Diego, California, USA.
156
Department of Radiology, University of California, San Diego, California, USA.
157
Department of Psychiatry, University of California, San Diego, California, USA.
158
Department of Cognitive Science, University of California, San Diego, California, USA.
159
Avera Institute for Human Genetics, Sioux Falls, South Dakota, USA.
160
Program in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA.
161
Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
162
Broad Institute, Cambridge, Massachusetts, USA.
163
Faculty of Health and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Australia.
164
Neurology Division, Beaumont Hospital, Dublin, 9, Ireland.
165
Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium.
166
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
167
Cognitive Genetics and Cognitive Therapy Group, Neuroimaging, Cognition and Genomics Centre (NICOG) and NCBES Galway Neuroscience Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
168
Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 8, Ireland.
169
Janssen Research and Development, LLC, Titusville, New Jersey, USA.
170
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin, Germany.
171
Intramural Research Program of the National Institute on Aging, Baltimore, Maryland, USA.
172
Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, USA.
173
Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK.
174
Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
175
University of Texas Health Science Center, San Antonio, Texas, USA.
176
Division of Cerebral Integration, National Institute for Physiological Sciences, Aichi, Japan.
177
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
178
Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
179
Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan.
180
Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
181
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
182
Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
183
Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA.
184
HMNC Brain Health, Munich, Germany.
185
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
186
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.
187
Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
188
NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland, USA.
189
School of Psychology, University of Sussex, Brighton, UK.
190
Institute of Cognitive Neuroscience, University College London, London, UK.
191
Department of Neuroinformatics, Araya Brain Imaging, Tokyo, Japan.
192
Medical University of Lodz, Lodz, Poland.
193
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
194
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
195
Neuroscience Research Australia, Sydney, Australia.
196
School of Medical Sciences, UNSW, Sydney, Australia.
197
Columbia University Medical Center, New York, New York, USA.
198
Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
199
Department of Neurology, University of Washington, Seattle, Washington, USA.
200
Department of Epidemiology, University of Washington, Seattle, Washington, USA.
201
Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
202
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
203
Department of Psychiatry, University of Oxford, Oxford, UK.
204
NIHR Dementia Biomedical Research Unit, King's College London, London, UK.
205
Imaging of Dementia and Aging (IDeA) Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, California, USA.
206
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
207
Centre for Advanced Imaging, University of Queensland, Brisbane, Australia.
208
Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy.
209
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
210
University of Liverpool, Institute of Translational Medicine, Liverpool, UK.
211
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
212
German Center for Cardiovascular Research (DZHK e.V.), partner site Greifswald, Germany.
213
Department of Statistics and Warwick Manufacturing Group, University of Warwick, Coventry, UK.
214
Department of Medical Informatics Erasmus MC, Rotterdam, the Netherlands.
215
Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands.
216
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
217
Rotman Research Institute, University of Toronto, Toronto, Canada.
218
Departments of Psychology and Psychiatry, University of Toronto, Canada.
219
Child Mind Institute, New York, New York, USA.
220
Department of Physiology, University of Toronto, Toronto, Canada.
221
Department of Nutritional Sciences, University of Toronto, Toronto, Canada.
222
Department of Radiology, University of Calgary, Calgary, Canada.
223
Department of Clinical Neuroscience, University of Calgary, Calgary, Canada.
224
Department of Medicine, University of Washington, Seattle, Washington, USA.
225
Department of Health Services, University of Washington, Seattle, Washington, USA.
226
Group Health Research Institute, Group Health, Seattle, Washington, USA.
227
Department of Developmental Disability Neuropsychiatry, School of Psychiatry, UNSW Medicine, Australia.
228
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Pediatrics at Harbor-UCLA Medical Center, Torrance, California, USA.
229
Evelyn F. McKnight Brain Institute, University of Miami, Miller School of Medicine, Miami, Florida, USA.
230
Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia.
231
Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK.
232
Biomedical Research Centre for Mental Health, King's College London, London, UK.
233
Biomedical Research Unit for Dementia, King's College London, London, UK.
234
MRC Edinburgh Brain Bank, University of Edinburgh, Academic Department of Neuropathology, Centre for Clinical Brain Sciences, Edinburgh, UK.
235
Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.
236
Neurocentre Neurology, Kuopio University Hospital, Finland.
237
Department of Medicine, Peninsula Health and Monash University, Melbourne, Australia.
238
Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, UK.
239
Laboratory of Neuro Imaging, Institute for Neuroimaging and Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
240
Brain Resource Center, Johns Hopkins University, Baltimore, Maryland, USA.
241
Georgia State University, Atlanta, Georgia, USA.
242
Institute for Neurodegenerative Disorders, UMR 5293, CEA, CNRS, Université de Bordeaux, France.
243
Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
244
Genentech Inc., South San Francisco, California, USA.
245
Department of Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden, The Netherlands.
246
Neuroimaging Centre, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
247
Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
248
Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
249
Center for Imaging of Neurodegenerative Disease, San Francisco VA Medical Center, University of California, San Francisco, California, USA.
250
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
251
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
252
Institute of Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria.
253
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
254
Intramural Research Program, NIA, NIH, Bethesda, Maryland, USA.
255
Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA.
256
Department of Neurology, Bordeaux University Hospital, Bordeaux, France.
257
Department of Neurology, Erasmus MC, Rotterdam, the Netherlands.

Abstract

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

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