Common genetic variants influence human subcortical brain structures.
Journal: Nature
Volume: 520
Issue: 7546
Year of Publication: 2015
Affiliated Institutions: Imaging Genetics Center, Institute for Neuroimaging &Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California , USA. ] Imaging Genetics Center, Institute for Neuroimaging &Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California , USA. [] Neurogenetics Program, Department of Neurology, UCLA School of Medicine, Los Angeles, California , USA. QIMR Berghofer Medical Research Institute, Brisbane , Australia. ] Department of Human Genetics, Radboud university medical center, Nijmegen HB, The Netherlands. [] Department of Psychiatry, Radboud university medical center, Nijmegen HB, The Netherlands. [] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen HB, The Netherlands. [] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen GL, The Netherlands. MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE AF, UK. ] Laboratory of Human Genetics and Cognitive Functions, Institut Pasteur, Paris , France. [] Centre Nationale de Recherche Scientifique (CNRS) Unité de Recherche Associée (URA) Genes, Synapses and Cognition, Institut Pasteur, Paris , France. [] Université Paris Diderot, Sorbonne Paris Cité, Paris , France. ] German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald , Germany. [] Department of Psychiatry, University Medicine Greifswald, Greifswald , Germany. Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, CX, The Netherlands. Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå , Sweden. ] Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH XU, UK. [] Department of Computer Science, Lagos State University, Lagos, Nigeria. [] Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH XU, UK. ] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney , Australia. [] School of Mathematics and Statistics, University of Sydney, Sydney , Australia. The Hospital for Sick Children, University of Toronto, Toronto MG X, Canada. ] Department of Human Genetics, Radboud university medical center, Nijmegen HB, The Netherlands. [] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen HB, The Netherlands. [] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen GL, The Netherlands. ] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-, Norway. [] NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo , Norway. ] Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal HH R, Canada. [] Department of Psychiatry and Biomedical Engineering, McGill University, Montreal HA B, Canada. Lieber Institute for Brain Development, Baltimore, Maryland , USA. ] Imaging Genetics Center, Institute for Neuroimaging &Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California , USA. [] Interdepartmental Neuroscience Graduate Program, UCLA School of Medicine, Los Angeles, California , USA. Biological Psychology, Neuroscience Campus Amsterdam &EMGO Institute for Health and Care Research, VU University &VU Medical Center, Amsterdam BT, The Netherlands. ] NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway. [] Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen , Norway. Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, Mannheim , Germany. ] Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen XD, The Netherlands. [] International Max Planck Research School for Language Sciences, Nijmegen XD, The Netherlands. Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden Germany. Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland , USA. ] Department of Psychology, Yale University, New Haven, Connecticut , USA. [] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts , USA. ] Department of Human Genetics, Radboud university medical center, Nijmegen HB, The Netherlands. [] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen GL, The Netherlands. Department of Psychiatry, University Medicine Greifswald, Greifswald , Germany. ] Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana , USA. [] Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana , USA. [] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana , USA. Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen , Germany. ] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts , USA. [] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts , USA. [] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts , USA. [] Department of Psychiatry, Harvard Medical School, Boston, Massachusetts , USA. Center for Neurobehavioral Genetics, University of California, Los Angeles, California , USA. Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH JZ, UK. Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney , Australia. ] Department of Biomedicine, Aarhus University, Aarhus DK-, Denmark. [] The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen DK-, Denmark. [] Center for integrated Sequencing, iSEQ, Aarhus University, Aarhus DK-, Denmark. Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam HL, The Netherlands. Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH HF, UK. ] Department of Medical and Molecular Genetics, King's College London, London SE RT, UK. [] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WCN BG, UK. ] Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana , USA. [] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana , USA. ] Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander , Spain. [] Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid , Spain. ] Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin , Ireland. [] Center for Translational Research on Adversity, Neurodevelopment and Substance Abuse (C-TRANS), Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland , USA. ] Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå , Sweden. [] Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden. Max Planck Institute of Psychiatry, Munich , Germany. ] Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, California , USA. [] Department of Cognitive Sciences, University of California, San Diego, California , USA. ] QIMR Berghofer Medical Research Institute, Brisbane , Australia. [] School of Psychology, University of Queensland, Brisbane , Australia. [] Centre for Advanced Imaging, University of Queensland, Brisbane , Australia. Institute for Community Medicine, University Medicine Greifswald, Greifswald D-, Germany. ] Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts , USA. [] Medical and Population Genetics Program, Broad Institute of Harvard and MIT, Boston, Massachusetts , USA. ] NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo , Norway. [] Department of Psychology, University of Oslo, Oslo , Norway. ] The Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, Oxford University, Oxford OX DU, UK. [] Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut , USA. Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen GL, The Netherlands. Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal HA B, Canada. ] Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden Germany. [] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts , USA. [] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts , USA. ] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-, Norway. [] Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo , Norway. NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-, Norway. ] UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WCN BG, UK. [] Department of Medicine, Imperial College London, London W NN, UK. Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WCN BG, UK. ] Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut , USA. [] Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut , USA. Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin , Ireland. ] Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH XU, UK. [] Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH JZ, UK. [] Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH XU, UK. ] Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH HF, UK. [] Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut , USA. [] Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut , USA. ] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WCN BG, UK. [] Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh , Saudi Arabia. ] Texas Biomedical Research Institute, San Antonio, Texas , USA. [] University of Texas Health Science Center, San Antonio, Texas , USA. ] National Ageing Research Institute, Royal Melbourne Hospital, Melbourne , Australia. [] Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne , Australia. Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland , USA. ] Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH XU, UK. [] Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH XU, UK. [] Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH JZ, UK. [] Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH XU, UK. N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow , Russia. Texas Biomedical Research Institute, San Antonio, Texas , USA. ] Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel , Switzerland. [] Institute of Human Genetics, University of Bonn, Bonn, D-, Germany. [] Institute of Neuroscience and Medicine (INM-), Research Centre Jülich, Jülich, D-, Germany. [] Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-, Germany. School of Psychology, University of Queensland, Brisbane , Australia. Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin , Germany. Clinical Research Branch, National Institute on Aging, Baltimore, Maryland , USA. ] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana , USA. [] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana , USA. ] University of Texas Health Science Center, San Antonio, Texas , USA. [] South Texas Veterans Health Care System, San Antonio, Texas , USA. Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Osaka -, Japan. ] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WCN BG, UK. [] Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne , Australia. ] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts , USA. [] Harvard Medical School, Boston, Massachusetts , USA. Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WCN BG, UK. Department of Psychiatry, University of Groningen, University Medical Center Groningen, GZ Groningen, The Netherlands. Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald , Germany. Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-, Germany. Departments of Cognitive and Clinical Neuropsychology, VU University Amsterdam, BT Amsterdam, The Netherlands. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald , Germany. Department of Psychiatry, Fujita Health University School of Medicine, Toyoake -, Japan. Radiology, Mayo Clinic, Rochester, Minnesota , USA. FMRIB Centre, University of Oxford, Oxford OX DU, UK. NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland , USA. ] School of Psychology, University of Sussex, Brighton BN QH, UK. [] Institute of Cognitive Neuroscience, University College London, London WCN AR, UK. Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland, Baltimore, Maryland , USA. ] Neuroscience Research Australia, Sydney , Australia. [] School of Medical Sciences, UNSW, Sydney , Australia. ] Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland , USA. [] Department of Pathology and Cell Biology, Columbia University Medical Center, New York , USA. Lymphocyte Cell Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland , USA. Centre for Advanced Imaging, University of Queensland, Brisbane , Australia. Department of Psychiatry, Ludwig-Maximilians-Universität, Munich , Germany. ] Institute of Human Genetics, University of Bonn, Bonn, D-, Germany. [] Institute of Neuroscience and Medicine (INM-), Research Centre Jülich, Jülich, D-, Germany. [] Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-, Germany. ] FMRIB Centre, University of Oxford, Oxford OX DU, UK. [] Department of Statistics &WMG, University of Warwick, Coventry CV AL, UK. ] Institute of Human Genetics, University of Bonn, Bonn, D-, Germany. [] Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-, Germany. Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka -, Japan. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana , USA. ] Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid , Spain. [] Institute of Psychiatry, King's College London, London SE AF, UK. ] Department of Neurology, University of Calgary, Calgary TN T, Canada. [] Department of Clinical Neuroscience, University of Calgary, Calgary TN T, Canada. Psychiatry and Human Behavior, University of California, Irvine, California , USA. Department of Psychology, University of Oslo, Oslo , Norway. ] Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts , USA. [] Harvard Medical School, Boston, Massachusetts , USA. Department of General Psychiatry, Heidelberg University Hospital, Heidelberg , Germany. Department of Neuropathology, MRC Sudden Death Brain Bank Project, University of Edinburgh, Edinburgh EH AG, UK. Laboratory of Neuro Imaging, Institute for Neuroimaging and Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California , USA. Department of Pathology, Johns Hopkins University, Baltimore, Maryland , USA. Psychology Department and Neuroscience Institute, Georgia State University, Atlanta, Georgia , USA. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH XU, UK. Genentech, South San Francisco, California , USA. Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden ZA, The Netherlands. Neuroimaging Centre, University of Groningen, University Medical Center Groningen, Groningen AW, The Netherlands. Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa , USA. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm SE- , Sweden. Behavioral Epidemiology Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland , USA. Faculty of Life Sciences, University of Manchester, Manchester M PT, UK. ] Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee , USA. [] Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee , USA. [] Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong , China. ] Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin , Ireland. [] Cognitive Genetics and Therapy Group, School of Psychology &Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland. ] Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee , USA. [] Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee , USA. ] Department of Human Genetics, Radboud university medical center, Nijmegen HB, The Netherlands. [] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen GL, The Netherlands. [] Department of Clinical Genetics, Maastricht University Medical Center, Maastricht MD, The Netherlands. ] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts , USA. [] Department of Psychology, Center for Brain Science, Harvard University, Boston, Massachusetts , USA. ] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen HB, The Netherlands. [] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen GL, The Netherlands. [] Karakter Child and Adolescent Psychiatry, Radboud university medical center, Nijmegen HB, The Netherlands. ] The Mind Research Network &LBERI, Albuquerque, New Mexico , USA. [] Department of ECE, University of New Mexico, Albuquerque, New Mexico , USA. ] Center for Translational Imaging and Personalized Medicine, University of California, San Diego, California , USA. [] Departments of Neurosciences, Radiology, Psychiatry, and Cognitive Science, University of California, San Diego, California , USA. Avera Institute for Human Genetics, Sioux Falls, South Dakota, , USA. ] Molecular and Cellular Therapeutics, The Royal College of Surgeons, Dublin , Ireland. [] Neurology Division, Beaumont Hospital, Dublin , Ireland. Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels , Belgium. ] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-, Norway. [] Department of Medical Genetics, Oslo University Hospital, Oslo , Norway. ] Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland , USA. [] Janssen Research &Development, Johnson &Johnson, Titusville, New Jersey , USA. ] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts , USA. [] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts , USA. [] Harvard Medical School, Boston, Massachusetts , USA. Department of Psychiatry, University of Iowa, Iowa City, Iowa , USA. ] German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald , Germany. [] Institute for Community Medicine, University Medicine Greifswald, Greifswald D-, Germany. ] Max Planck Institute of Psychiatry, Munich , Germany. [] Munich Cluster for Systems Neurology (SyNergy), Munich , Germany. [] University of Liverpool, Institute of Translational Medicine, Liverpool L BX, UK. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald , Germany. Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts , USA. UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WCN BG, UK. ] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts , USA. [] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts , USA. [] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts , USA. [] Harvard Medical School, Boston, Massachusetts , USA. Center for Imaging of Neurodegenerative Disease, San Francisco VA Medical Center, University of California, San Francisco, California , USA. ] Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam CB, The Netherlands. [] Department of Radiology, Erasmus University Medical Centre, Rotterdam CN, The Netherlands. ] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-, Norway. [] Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo , Norway. [] Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm SE- , Sweden. ] Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland , USA. [] Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. ] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen HB, The Netherlands. [] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen GL, The Netherlands. ] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen GL, The Netherlands. [] Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen XD, The Netherlands. ] Department of Psychiatry, University Medicine Greifswald, Greifswald , Germany. [] Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund , Germany. ] Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen , Germany. [] Max Planck Institute of Psychiatry, Munich , Germany. Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka -, Japan. ] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-, Norway. [] Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm SE- , Sweden. Medical University of Lodz, Lodz -, Poland. ] Department of Psychiatry, University of Oxford, Oxford OX JX, UK. [] NIHR Dementia Biomedical Research Unit, King's College London, London SE AF, UK. ] Lieber Institute for Brain Development, Baltimore, Maryland , USA. [] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland , USA. Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia , Italy. Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. ] Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH JZ, UK. [] Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH HF, UK. ] Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, CX, The Netherlands. [] Center for Neurobehavioral Genetics, University of California, Los Angeles, California , USA. ] Rotman Research Institute, University of Toronto, Toronto MA E, Canada. [] Departments of Psychology and Psychiatry, University of Toronto, Toronto MT R, Canada. ] The Hospital for Sick Children, University of Toronto, Toronto MG X, Canada. [] Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto MS E, Canada. ] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WCN BG, UK. [] Department of Medical and Molecular Genetics, King's College London, London SE RT, UK. ] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney , Australia. [] Neuropsychiatric Institute, Prince of Wales Hospital, Sydney , Australia. ] Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana , USA. [] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana , USA. [] Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin , Germany. ] Department of Neuroimaging, Institute of Psychiatry, King's College London, London SE AF, UK. [] Biomedical Research Centre for Mental Health, King's College London, London SE AF, UK. [] Biomedical Research Unit for Dementia, King's College London, London SE AF, UK. ] Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio FI-, Finland. [] Neurocentre Neurology, Kuopio University Hospital, Kuopio FI-, Finland. Department of Medical and Molecular Genetics, King's College London, London SE RT, UK. ] Lieber Institute for Brain Development, Baltimore, Maryland , USA. [] Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland , USA. ] Department of Radiology, Erasmus University Medical Centre, Rotterdam CN, The Netherlands. [] Department of Epidemiology, Erasmus University Medical Centre, Rotterdam CN, The Netherlands. Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, Maryland , USA. Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz , Austria. INSERM U, University of Bordeaux, Bordeaux , France. ] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts , USA. [] Framingham Heart Study, Framingham, Massachusetts , USA. ] Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania , USA. [] Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania , USA. [] Department of Psychology, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania , USA. General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland , USA. Department of Epidemiology, Erasmus University Medical Centre, Rotterdam CN, The Netherlands. ] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts , USA. [] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts , USA. ] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts , USA. [] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts , USA. [] Computer Science and AI Lab, Massachusetts Institute of Technology, Boston, Massachusetts , USA. Department of Neurology University of Washington, Seattle, Washington , USA. Institute of Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland , USA. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts , USA. Groupe d'Imagerie Neurofonctionnelle, UMR CNRS, CEA and University of Bordeaux, Bordeaux , France. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington , USA. Icelandic Heart Association, University of Iceland, Faculty of Medicine, Reykjavik , Iceland. ] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts , USA. [] Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania , USA. ] QIMR Berghofer Medical Research Institute, Brisbane , Australia. [] School of Psychology, University of Queensland, Brisbane , Australia. ] Department of Human Genetics, Radboud university medical center, Nijmegen HB, The Netherlands. [] Department of Psychiatry, Radboud university medical center, Nijmegen HB, The Netherlands. [] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen GL, The Netherlands.
Abstract summary
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.Authors & Co-authors: Hibar Derrek P DP Stein Jason L JL Renteria Miguel E ME Arias-Vasquez Alejandro A Desrivières Sylvane S Jahanshad Neda N Toro Roberto R Wittfeld Katharina K Abramovic Lucija L Andersson Micael M Aribisala Benjamin S BS Armstrong Nicola J NJ Bernard Manon M Bohlken Marc M MM Boks Marco P MP Bralten Janita J Brown Andrew A AA Chakravarty M Mallar MM Chen Qiang Q Ching Christopher R K CR Cuellar-Partida Gabriel G den Braber Anouk A Giddaluru Sudheer S Goldman Aaron L AL Grimm Oliver O Guadalupe Tulio T Hass Johanna J Woldehawariat Girma G Holmes Avram J AJ Hoogman Martine M Janowitz Deborah D Jia Tianye T Kim Sungeun S Klein Marieke M Kraemer Bernd B Lee Phil H PH Olde Loohuis Loes M LM Luciano Michelle M Macare Christine C Mather Karen A KA Mattheisen Manuel M Milaneschi Yuri Y Nho Kwangsik K Papmeyer Martina M Ramasamy Adaikalavan A Risacher Shannon L SL Roiz-Santiañez Roberto R Rose Emma J EJ Salami Alireza A Sämann Philipp G PG Schmaal Lianne L Schork Andrew J AJ Shin Jean J Strike Lachlan T LT Teumer Alexander A van Donkelaar Marjolein M J MM van Eijk Kristel R KR Walters Raymond K RK Westlye Lars T LT Whelan Christopher D CD Winkler Anderson M AM Zwiers Marcel P MP Alhusaini Saud S Athanasiu Lavinia L Ehrlich Stefan S Hakobjan Marina M H MM Hartberg Cecilie B CB Haukvik Unn K UK Heister Angelien J G A M AJ Hoehn David D Kasperaviciute Dalia D Liewald David C M DC Lopez Lorna M LM Makkinje Remco R R RR Matarin Mar M Naber Marlies A M MA McKay D Reese DR Needham Margaret M Nugent Allison C AC Pütz Benno B Royle Natalie A NA Shen Li L Sprooten Emma E Trabzuni Daniah D van der Marel Saskia S L SS van Hulzen Kimm J E KJ Walton Esther E Wolf Christiane C Almasy Laura L Ames David D Arepalli Sampath S Assareh Amelia A AA Bastin Mark E ME Brodaty Henry H Bulayeva Kazima B KB Carless Melanie A MA Cichon Sven S Corvin Aiden A Curran Joanne E JE Czisch Michael M de Zubicaray Greig I GI Dillman Allissa A Duggirala Ravi R Dyer Thomas D TD Erk Susanne S Fedko Iryna O IO Ferrucci Luigi L Foroud Tatiana M TM Fox Peter T PT Fukunaga Masaki M Gibbs J Raphael JR Göring Harald H H HH Green Robert C RC Guelfi Sebastian S Hansell Narelle K NK Hartman Catharina A CA Hegenscheid Katrin K Heinz Andreas A Hernandez Dena G DG Heslenfeld Dirk J DJ Hoekstra Pieter J PJ Holsboer Florian F Homuth Georg G Hottenga Jouke-Jan JJ Ikeda Masashi M Jack Clifford R CR Jenkinson Mark M Johnson Robert R Kanai Ryota R Keil Maria M Kent Jack W JW Kochunov Peter P Kwok John B JB Lawrie Stephen M SM Liu Xinmin X Longo Dan L DL McMahon Katie L KL Meisenzahl Eva E Melle Ingrid I Mohnke Sebastian S Montgomery Grant W GW Mostert Jeanette C JC Mühleisen Thomas W TW Nalls Michael A MA Nichols Thomas E TE Nilsson Lars G LG Nöthen Markus M MM Ohi Kazutaka K Olvera Rene L RL Perez-Iglesias Rocio R Pike G Bruce GB Potkin Steven G SG Reinvang Ivar I Reppermund Simone S Rietschel Marcella M Romanczuk-Seiferth Nina N Rosen Glenn D GD Rujescu Dan D Schnell Knut K Schofield Peter R PR Smith Colin C Steen Vidar M VM Sussmann Jessika E JE Thalamuthu Anbupalam A Toga Arthur W AW Traynor Bryan J BJ Troncoso Juan J Turner Jessica A JA Valdés Hernández Maria C MC van 't Ent Dennis D van der Brug Marcel M van der Wee Nic J A NJ van Tol Marie-Jose MJ Veltman Dick J DJ Wassink Thomas H TH Westman Eric E Zielke Ronald H RH Zonderman Alan B AB Ashbrook David G DG Hager Reinmar R Lu Lu L McMahon Francis J FJ Morris Derek W DW Williams Robert W RW Brunner Han G HG Buckner Randy L RL Buitelaar Jan K JK Cahn Wiepke W Calhoun Vince D VD Cavalleri Gianpiero L GL Crespo-Facorro Benedicto B Dale Anders M AM Davies Gareth E GE Delanty Norman N Depondt Chantal C Djurovic Srdjan S Drevets Wayne C WC Espeseth Thomas T Gollub Randy L RL Ho Beng-Choon BC Hoffmann Wolfgang W Hosten Norbert N Kahn René S RS Le Hellard Stephanie S Meyer-Lindenberg Andreas A Müller-Myhsok Bertram B Nauck Matthias M Nyberg Lars L Pandolfo Massimo M Penninx Brenda W J H BW Roffman Joshua L JL Sisodiya Sanjay M SM Smoller Jordan W JW van Bokhoven Hans H van Haren Neeltje E M NE Völzke Henry H Walter Henrik H Weiner Michael W MW Wen Wei W White Tonya T Agartz Ingrid I Andreassen Ole A OA Blangero John J Boomsma Dorret I DI Brouwer Rachel M RM Cannon Dara M DM Cookson Mark R MR de Geus Eco J C EJ Deary Ian J IJ Donohoe Gary G Fernández Guillén G Fisher Simon E SE Francks Clyde C Glahn David C DC Grabe Hans J HJ Gruber Oliver O Hardy John J Hashimoto Ryota R Hulshoff Pol Hilleke E HE Jönsson Erik G EG Kloszewska Iwona I Lovestone Simon S Mattay Venkata S VS Mecocci Patrizia P McDonald Colm C McIntosh Andrew M AM Ophoff Roel A RA Paus Tomas T Pausova Zdenka Z Ryten Mina M Sachdev Perminder S PS Saykin Andrew J AJ Simmons Andy A Singleton Andrew A Soininen Hilkka H Wardlaw Joanna M JM Weale Michael E ME Weinberger Daniel R DR Adams Hieab H H HH Launer Lenore J LJ Seiler Stephan S Schmidt Reinhold R Chauhan Ganesh G Satizabal Claudia L CL Becker James T JT Yanek Lisa L van der Lee Sven J SJ Ebling Maritza M Fischl Bruce B Longstreth W T WT Greve Douglas D Schmidt Helena H Nyquist Paul P Vinke Louis N LN van Duijn Cornelia M CM Xue Luting L Mazoyer Bernard B Bis Joshua C JC Gudnason Vilmundur V Seshadri Sudha S Ikram M Arfan MA Martin Nicholas G NG Wright Margaret J MJ Schumann Gunter G Franke Barbara B Thompson Paul M PM Medland Sarah E SE
Study Outcome
Source Link: Visit source
Statistics
Citations : Blokland GA, de Zubicaray GI, McMahon KL, Wright MJ. Genetic and environmental influences on neuroimaging phenotypes: a meta-analytical perspective on twin imaging studies. Twin Res Hum Genet. 2012;15:351–371.Authors : 292
Identifiers
Doi : 10.1038/nature14101SSN : 1476-4687