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    Publication Date: 2015-01-22
    Description: 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 x 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393366/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393366/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hibar, Derrek P -- Stein, Jason L -- Renteria, Miguel E -- Arias-Vasquez, Alejandro -- Desrivieres, Sylvane -- Jahanshad, Neda -- Toro, Roberto -- Wittfeld, Katharina -- Abramovic, Lucija -- Andersson, Micael -- Aribisala, Benjamin S -- Armstrong, Nicola J -- Bernard, Manon -- Bohlken, Marc M -- Boks, Marco P -- Bralten, Janita -- Brown, Andrew A -- Chakravarty, M Mallar -- Chen, Qiang -- Ching, Christopher R K -- Cuellar-Partida, Gabriel -- den Braber, Anouk -- Giddaluru, Sudheer -- Goldman, Aaron L -- Grimm, Oliver -- Guadalupe, Tulio -- Hass, Johanna -- Woldehawariat, Girma -- Holmes, Avram J -- Hoogman, Martine -- Janowitz, Deborah -- Jia, Tianye -- Kim, Sungeun -- Klein, Marieke -- Kraemer, Bernd -- Lee, Phil H -- Olde Loohuis, Loes M -- Luciano, Michelle -- Macare, Christine -- Mather, Karen A -- Mattheisen, Manuel -- Milaneschi, Yuri -- Nho, Kwangsik -- Papmeyer, Martina -- Ramasamy, Adaikalavan -- Risacher, Shannon L -- Roiz-Santianez, Roberto -- Rose, Emma J -- Salami, Alireza -- Samann, Philipp G -- Schmaal, Lianne -- Schork, Andrew J -- Shin, Jean -- Strike, Lachlan T -- Teumer, Alexander -- van Donkelaar, Marjolein M J -- van Eijk, Kristel R -- Walters, Raymond K -- Westlye, Lars T -- Whelan, Christopher D -- Winkler, Anderson M -- Zwiers, Marcel P -- Alhusaini, Saud -- Athanasiu, Lavinia -- Ehrlich, Stefan -- Hakobjan, Marina M H -- Hartberg, Cecilie B -- Haukvik, Unn K -- Heister, Angelien J G A M -- Hoehn, David -- Kasperaviciute, Dalia -- Liewald, David C M -- Lopez, Lorna M -- Makkinje, Remco R R -- Matarin, Mar -- Naber, Marlies A M -- McKay, D Reese -- Needham, Margaret -- Nugent, Allison C -- Putz, Benno -- Royle, Natalie A -- Shen, Li -- Sprooten, Emma -- Trabzuni, Daniah -- van der Marel, Saskia S L -- van Hulzen, Kimm J E -- Walton, Esther -- Wolf, Christiane -- Almasy, Laura -- Ames, David -- Arepalli, Sampath -- Assareh, Amelia A -- Bastin, Mark E -- Brodaty, Henry -- Bulayeva, Kazima B -- Carless, Melanie A -- Cichon, Sven -- Corvin, Aiden -- Curran, Joanne E -- Czisch, Michael -- de Zubicaray, Greig I -- Dillman, Allissa -- Duggirala, Ravi -- Dyer, Thomas D -- Erk, Susanne -- Fedko, Iryna O -- Ferrucci, Luigi -- Foroud, Tatiana M -- Fox, Peter T -- Fukunaga, Masaki -- Gibbs, J Raphael -- Goring, Harald H H -- Green, Robert C -- Guelfi, Sebastian -- Hansell, Narelle K -- Hartman, Catharina A -- Hegenscheid, Katrin -- Heinz, Andreas -- Hernandez, Dena G -- Heslenfeld, Dirk J -- Hoekstra, Pieter J -- Holsboer, Florian -- Homuth, Georg -- Hottenga, Jouke-Jan -- Ikeda, Masashi -- Jack, Clifford R Jr -- Jenkinson, Mark -- Johnson, Robert -- Kanai, Ryota -- Keil, Maria -- Kent, Jack W Jr -- Kochunov, Peter -- Kwok, John B -- Lawrie, Stephen M -- Liu, Xinmin -- Longo, Dan L -- McMahon, Katie L -- Meisenzahl, Eva -- Melle, Ingrid -- Mohnke, Sebastian -- Montgomery, Grant W -- Mostert, Jeanette C -- Muhleisen, Thomas W -- Nalls, Michael A -- Nichols, Thomas E -- Nilsson, Lars G -- Nothen, Markus M -- Ohi, Kazutaka -- Olvera, Rene L -- Perez-Iglesias, Rocio -- Pike, G Bruce -- Potkin, Steven G -- Reinvang, Ivar -- Reppermund, Simone -- Rietschel, Marcella -- Romanczuk-Seiferth, Nina -- Rosen, Glenn D -- Rujescu, Dan -- Schnell, Knut -- Schofield, Peter R -- Smith, Colin -- Steen, Vidar M -- Sussmann, Jessika E -- Thalamuthu, Anbupalam -- Toga, Arthur W -- Traynor, Bryan J -- Troncoso, Juan -- Turner, Jessica A -- Valdes Hernandez, Maria C -- van 't Ent, Dennis -- van der Brug, Marcel -- van der Wee, Nic J A -- van Tol, Marie-Jose -- Veltman, Dick J -- Wassink, Thomas H -- Westman, Eric -- Zielke, Ronald H -- Zonderman, Alan B -- Ashbrook, David G -- Hager, Reinmar -- Lu, Lu -- McMahon, Francis J -- Morris, Derek W -- Williams, Robert W -- Brunner, Han G -- Buckner, Randy L -- Buitelaar, Jan K -- Cahn, Wiepke -- Calhoun, Vince D -- Cavalleri, Gianpiero L -- Crespo-Facorro, Benedicto -- Dale, Anders M -- Davies, Gareth E -- Delanty, Norman -- Depondt, Chantal -- Djurovic, Srdjan -- Drevets, Wayne C -- Espeseth, Thomas -- Gollub, Randy L -- Ho, Beng-Choon -- Hoffmann, Wolfgang -- Hosten, Norbert -- Kahn, Rene S -- Le Hellard, Stephanie -- Meyer-Lindenberg, Andreas -- Muller-Myhsok, Bertram -- Nauck, Matthias -- Nyberg, Lars -- Pandolfo, Massimo -- Penninx, Brenda W J H -- Roffman, Joshua L -- Sisodiya, Sanjay M -- Smoller, Jordan W -- van Bokhoven, Hans -- van Haren, Neeltje E M -- Volzke, Henry -- Walter, Henrik -- Weiner, Michael W -- Wen, Wei -- White, Tonya -- Agartz, Ingrid -- Andreassen, Ole A -- Blangero, John -- Boomsma, Dorret I -- Brouwer, Rachel M -- Cannon, Dara M -- Cookson, Mark R -- de Geus, Eco J C -- Deary, Ian J -- Donohoe, Gary -- Fernandez, Guillen -- Fisher, Simon E -- Francks, Clyde -- Glahn, David C -- Grabe, Hans J -- Gruber, Oliver -- Hardy, John -- Hashimoto, Ryota -- Hulshoff Pol, Hilleke E -- Jonsson, Erik G -- Kloszewska, Iwona -- Lovestone, Simon -- Mattay, Venkata S -- Mecocci, Patrizia -- McDonald, Colm -- McIntosh, Andrew M -- Ophoff, Roel A -- Paus, Tomas -- Pausova, Zdenka -- Ryten, Mina -- Sachdev, Perminder S -- Saykin, Andrew J -- Simmons, Andy -- Singleton, Andrew -- Soininen, Hilkka -- Wardlaw, Joanna M -- Weale, Michael E -- Weinberger, Daniel R -- Adams, Hieab H H -- Launer, Lenore J -- Seiler, Stephan -- Schmidt, Reinhold -- Chauhan, Ganesh -- Satizabal, Claudia L -- Becker, James T -- Yanek, Lisa -- van der Lee, Sven J -- Ebling, Maritza -- Fischl, Bruce -- Longstreth, W T Jr -- Greve, Douglas -- Schmidt, Helena -- Nyquist, Paul -- Vinke, Louis N -- van Duijn, Cornelia M -- Xue, Luting -- Mazoyer, Bernard -- Bis, Joshua C -- Gudnason, Vilmundur -- Seshadri, Sudha -- Ikram, M Arfan -- Alzheimer's Disease Neuroimaging Initiative -- CHARGE Consortium -- EPIGEN -- IMAGEN -- SYS -- Martin, Nicholas G -- Wright, Margaret J -- Schumann, Gunter -- Franke, Barbara -- Thompson, Paul M -- Medland, Sarah E -- 100309/Wellcome Trust/United Kingdom -- 104036/Wellcome Trust/United Kingdom -- BB/F019394/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0700704/Medical Research Council/United Kingdom -- G0701120/Medical Research Council/United Kingdom -- G1001245/Medical Research Council/United Kingdom -- K99 LM011384/LM/NLM NIH HHS/ -- K99 MH101367/MH/NIMH NIH HHS/ -- MR/K026992/1/Medical Research Council/United Kingdom -- P41 EB015922/EB/NIBIB NIH HHS/ -- P50 AG005133/AG/NIA NIH HHS/ -- P50 AG005134/AG/NIA NIH HHS/ -- P50 AG005146/AG/NIA NIH HHS/ -- R00 LM011384/LM/NLM NIH HHS/ -- R01 AG040060/AG/NIA NIH HHS/ -- R01 EB015611/EB/NIBIB NIH HHS/ -- RF1 AG041915/AG/NIA NIH HHS/ -- U01 AG049505/AG/NIA NIH HHS/ -- U24 AG021886/AG/NIA NIH HHS/ -- U54 EB020403/EB/NIBIB NIH HHS/ -- UL1 TR001108/TR/NCATS NIH HHS/ -- UL1 TR001120/TR/NCATS NIH HHS/ -- England -- Nature. 2015 Apr 9;520(7546):224-9. doi: 10.1038/nature14101. Epub 2015 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Imaging Genetics Center, Institute for Neuroimaging &Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90292, USA. ; 1] Imaging Genetics Center, Institute for Neuroimaging &Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90292, USA. [2] Neurogenetics Program, Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095, USA. ; QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [3] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [4] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK. ; 1] Laboratory of Human Genetics and Cognitive Functions, Institut Pasteur, Paris 75015, France. [2] Centre Nationale de Recherche Scientifique (CNRS) Unite de Recherche Associee (URA) 2182 Genes, Synapses and Cognition, Institut Pasteur, Paris 75015, France. [3] Universite Paris Diderot, Sorbonne Paris Cite, Paris 75015, France. ; 1] German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany. [2] Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany. ; Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands. ; Umea Centre for Functional Brain Imaging (UFBI), Umea University, Umea 901 87, Sweden. ; 1] Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK. [2] Department of Computer Science, Lagos State University, Lagos, Nigeria. [3] Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. ; 1] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia. [2] School of Mathematics and Statistics, University of Sydney, Sydney 2006, Australia. ; The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [3] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway. ; 1] Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal H4H 1R3, Canada. [2] Department of Psychiatry and Biomedical Engineering, McGill University, Montreal H3A 2B4, Canada. ; Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA. ; 1] Imaging Genetics Center, Institute for Neuroimaging &Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90292, USA. [2] Interdepartmental Neuroscience Graduate Program, UCLA School of Medicine, Los Angeles, California 90095, USA. ; Biological Psychology, Neuroscience Campus Amsterdam &EMGO Institute for Health and Care Research, VU University &VU Medical Center, Amsterdam 1081 BT, The Netherlands. ; 1] NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway. [2] Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen 5021, Norway. ; Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, Mannheim 68159, Germany. ; 1] Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands. [2] International Max Planck Research School for Language Sciences, Nijmegen 6525 XD, The Netherlands. ; Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden 01307 Germany. ; Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA. ; 1] Department of Psychology, Yale University, New Haven, Connecticut 06511, USA. [2] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany. ; 1] Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [2] Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [3] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany. ; 1] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [3] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts 02141, USA. [4] Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA. ; Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. ; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia. ; 1] Department of Biomedicine, Aarhus University, Aarhus DK-8000, Denmark. [2] The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen DK-8000, Denmark. [3] Center for integrated Sequencing, iSEQ, Aarhus University, Aarhus DK-8000, Denmark. ; Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands. ; Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK. ; 1] Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK. [2] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. ; 1] Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [2] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; 1] Department of Psychiatry, University Hospital Marques de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander 39008, Spain. [2] Cibersam (Centro Investigacion Biomedica en Red Salud Mental), Madrid 28029, Spain. ; 1] Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland. [2] Center for Translational Research on Adversity, Neurodevelopment and Substance Abuse (C-TRANS), Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland 21045, USA. ; 1] Umea Centre for Functional Brain Imaging (UFBI), Umea University, Umea 901 87, Sweden. [2] Aging Research Center, Karolinska Institutet and Stockholm University, 11330 Stockholm, Sweden. ; Max Planck Institute of Psychiatry, Munich 80804, Germany. ; 1] Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, California 92093, USA. [2] Department of Cognitive Sciences, University of California, San Diego, California 92161, USA. ; 1] QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. [2] School of Psychology, University of Queensland, Brisbane 4072, Australia. [3] Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia. ; Institute for Community Medicine, University Medicine Greifswald, Greifswald D-17475, Germany. ; 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [2] Medical and Population Genetics Program, Broad Institute of Harvard and MIT, Boston, Massachusetts 02142, USA. ; 1] NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway. [2] Department of Psychology, University of Oslo, Oslo 0373, Norway. ; 1] The Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, Oxford University, Oxford OX3 9DU, UK. [2] Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, USA. ; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada. ; 1] Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden 01307 Germany. [2] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [3] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway. ; NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. ; 1] UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK. [2] Department of Medicine, Imperial College London, London W12 0NN, UK. ; Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK. ; 1] Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, USA. [2] Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA. ; Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland. ; 1] Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK. [2] Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. [3] Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. ; 1] Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK. [2] Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, USA. [3] Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA. ; 1] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. [2] Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia. ; 1] Texas Biomedical Research Institute, San Antonio, Texas 78245, USA. [2] University of Texas Health Science Center, San Antonio, Texas 78229, USA. ; 1] National Ageing Research Institute, Royal Melbourne Hospital, Melbourne 3052, Australia. [2] Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia. ; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK. [2] Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. [3] Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. [4] Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. ; N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia. ; Texas Biomedical Research Institute, San Antonio, Texas 78245, USA. ; 1] Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel 4055, Switzerland. [2] Institute of Human Genetics, University of Bonn, Bonn, D-53127, Germany. [3] Institute of Neuroscience and Medicine (INM-1), Research Centre Julich, Julich, D-52425, Germany. [4] Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-53127, Germany. ; School of Psychology, University of Queensland, Brisbane 4072, Australia. ; Department of Psychiatry and Psychotherapy, Charite Universitatsmedizin Berlin, CCM, Berlin 10117, Germany. ; Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 20892, USA. ; 1] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [2] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; 1] University of Texas Health Science Center, San Antonio, Texas 78229, USA. [2] South Texas Veterans Health Care System, San Antonio, Texas 78229, USA. ; Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. ; 1] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. [2] Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia. ; 1] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. ; Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands. ; Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald 17475, Germany. ; Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-53127, Germany. ; Departments of Cognitive and Clinical Neuropsychology, VU University Amsterdam, 1081 BT Amsterdam, The Netherlands. ; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17489, Germany. ; Department of Psychiatry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan. ; Radiology, Mayo Clinic, Rochester, Minnesota 55905, USA. ; FMRIB Centre, University of Oxford, Oxford OX3 9DU, UK. ; NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland 21201, USA. ; 1] School of Psychology, University of Sussex, Brighton BN1 9QH, UK. [2] Institute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK. ; Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland, Baltimore, Maryland 21201, USA. ; 1] Neuroscience Research Australia, Sydney 2031, Australia. [2] School of Medical Sciences, UNSW, Sydney 2052, Australia. ; 1] Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA. [2] Department of Pathology and Cell Biology, Columbia University Medical Center, New York 10032, USA. ; Lymphocyte Cell Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. ; Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia. ; Department of Psychiatry, Ludwig-Maximilians-Universitat, Munich 80336, Germany. ; 1] Institute of Human Genetics, University of Bonn, Bonn, D-53127, Germany. [2] Institute of Neuroscience and Medicine (INM-1), Research Centre Julich, Julich, D-52425, Germany. [3] Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-53127, Germany. ; 1] FMRIB Centre, University of Oxford, Oxford OX3 9DU, UK. [2] Department of Statistics &WMG, University of Warwick, Coventry CV4 7AL, UK. ; 1] Institute of Human Genetics, University of Bonn, Bonn, D-53127, Germany. [2] Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-53127, Germany. ; Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan. ; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; 1] Cibersam (Centro Investigacion Biomedica en Red Salud Mental), Madrid 28029, Spain. [2] Institute of Psychiatry, King's College London, London SE5 8AF, UK. ; 1] Department of Neurology, University of Calgary, Calgary T2N 2T9, Canada. [2] Department of Clinical Neuroscience, University of Calgary, Calgary T2N 2T9, Canada. ; Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA. ; Department of Psychology, University of Oslo, Oslo 0373, Norway. ; 1] Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of General Psychiatry, Heidelberg University Hospital, Heidelberg 69115, Germany. ; Department of Neuropathology, MRC Sudden Death Brain Bank Project, University of Edinburgh, Edinburgh EH8 9AG, UK. ; Laboratory of Neuro Imaging, Institute for Neuroimaging and Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA. ; Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21287, USA. ; Psychology Department and Neuroscience Institute, Georgia State University, Atlanta, Georgia 30302, USA. ; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Genentech, South San Francisco, California 94080, USA. ; Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands. ; Neuroimaging Centre, University of Groningen, University Medical Center Groningen, Groningen 9713 AW, The Netherlands. ; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. ; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm SE-141 83, Sweden. ; Behavioral Epidemiology Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland 20892, USA. ; Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK. ; 1] Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. [2] Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. [3] Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China. ; 1] Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland. [2] Cognitive Genetics and Therapy Group, School of Psychology &Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland. ; 1] Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. [2] Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. [3] Department of Clinical Genetics, Maastricht University Medical Center, Maastricht 6200 MD, The Netherlands. ; 1] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [2] Department of Psychology, Center for Brain Science, Harvard University, Boston, Massachusetts 02138, USA. ; 1] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. [3] Karakter Child and Adolescent Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. ; 1] The Mind Research Network &LBERI, Albuquerque, New Mexico 87106, USA. [2] Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA. ; 1] Center for Translational Imaging and Personalized Medicine, University of California, San Diego, California 92093, USA. [2] Departments of Neurosciences, Radiology, Psychiatry, and Cognitive Science, University of California, San Diego, California 92093, USA. ; Avera Institute for Human Genetics, Sioux Falls, South Dakota, 57108, USA. ; 1] Molecular and Cellular Therapeutics, The Royal College of Surgeons, Dublin 2, Ireland. [2] Neurology Division, Beaumont Hospital, Dublin 9, Ireland. ; Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels 1070, Belgium. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] Department of Medical Genetics, Oslo University Hospital, Oslo 0450, Norway. ; 1] Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA. [2] Janssen Research &Development, Johnson &Johnson, Titusville, New Jersey 08560, USA. ; 1] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [2] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. [3] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242, USA. ; 1] German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany. [2] Institute for Community Medicine, University Medicine Greifswald, Greifswald D-17475, Germany. ; 1] Max Planck Institute of Psychiatry, Munich 80804, Germany. [2] Munich Cluster for Systems Neurology (SyNergy), Munich 81377, Germany. [3] University of Liverpool, Institute of Translational Medicine, Liverpool L69 3BX, UK. ; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald 17475, Germany. ; Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. ; UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK. ; 1] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [3] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts 02141, USA. [4] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Center for Imaging of Neurodegenerative Disease, San Francisco VA Medical Center, University of California, San Francisco, California 94121, USA. ; 1] Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam 3000 CB, The Netherlands. [2] Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway. [3] Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm SE-171 76, Sweden. ; 1] Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA. [2] Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. ; 1] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; 1] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. [2] Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands. ; 1] Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany. [2] Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund 18435, Germany. ; 1] Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany. [2] Max Planck Institute of Psychiatry, Munich 80804, Germany. ; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm SE-171 76, Sweden. ; Medical University of Lodz, Lodz 90-419, Poland. ; 1] Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK. [2] NIHR Dementia Biomedical Research Unit, King's College London, London SE5 8AF, UK. ; 1] Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA. [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia 06156, Italy. ; Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. ; 1] Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. [2] Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK. ; 1] Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands. [2] Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA. ; 1] Rotman Research Institute, University of Toronto, Toronto M6A 2E1, Canada. [2] Departments of Psychology and Psychiatry, University of Toronto, Toronto M5T 1R8, Canada. ; 1] The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada. [2] Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto M5S 3E2, Canada. ; 1] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. [2] Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK. ; 1] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia. [2] Neuropsychiatric Institute, Prince of Wales Hospital, Sydney 2031, Australia. ; 1] Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [2] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [3] Department of Psychiatry and Psychotherapy, Charite Universitatsmedizin Berlin, CCM, Berlin 10117, Germany. ; 1] Department of Neuroimaging, Institute of Psychiatry, King's College London, London SE5 8AF, UK. [2] Biomedical Research Centre for Mental Health, King's College London, London SE5 8AF, UK. [3] Biomedical Research Unit for Dementia, King's College London, London SE5 8AF, UK. ; 1] Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio FI-70211, Finland. [2] Neurocentre Neurology, Kuopio University Hospital, Kuopio FI-70211, Finland. ; Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK. ; 1] Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA. [2] Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; 1] Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands. [2] Department of Epidemiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands. ; Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, Maryland 20892, USA. ; Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria. ; INSERM U897, University of Bordeaux, Bordeaux 33076, France. ; 1] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. [2] Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; 1] Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. [2] Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. [3] Department of Psychology, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. ; General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Epidemiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands. ; 1] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. [2] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. ; 1] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. [2] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. [3] Computer Science and AI Lab, Massachusetts Institute of Technology, Boston, Massachusetts 02141, USA. ; Department of Neurology University of Washington, Seattle, Washington 98195, USA. ; Institute of Molecular Biology and Biochemistry, Medical University Graz, 8010 Graz, Austria. ; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; Groupe d'Imagerie Neurofonctionnelle, UMR5296 CNRS, CEA and University of Bordeaux, Bordeaux 33076, France. ; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA. ; Icelandic Heart Association, University of Iceland, Faculty of Medicine, Reykjavik 101, Iceland. ; 1] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. [2] Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. ; 1] QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. [2] School of Psychology, University of Queensland, Brisbane 4072, Australia. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [3] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25607358" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/genetics ; Apoptosis/genetics ; Brain/*anatomy & histology ; Caudate Nucleus/anatomy & histology ; Child ; Female ; Gene Expression Regulation, Developmental/genetics ; Genetic Loci/genetics ; Genetic Variation/*genetics ; *Genome-Wide Association Study ; Hippocampus/anatomy & histology ; Humans ; Magnetic Resonance Imaging ; Male ; Membrane Proteins/genetics ; Middle Aged ; Organ Size/genetics ; Putamen/anatomy & histology ; Sex Characteristics ; Skull/anatomy & histology ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
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    German Medical Science; Düsseldorf, Köln
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie; 70. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 92. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 47. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20061002-20061006; Berlin; DOCW.4.9.3-1112 /20060928/
    Publication Date: 2007-03-09
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 3
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    German Medical Science; Düsseldorf, Köln
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie; 70. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 92. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 47. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20061002-20061006; Berlin; DOCW.4.9.2-215 /20060928/
    Publication Date: 2007-03-09
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 4
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    German Medical Science; Düsseldorf, Köln
    In:  68. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 90. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 45. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20041019-20041023; Berlin; DOC04dguN5-533 /20041019/
    Publication Date: 2004-10-20
    Keywords: ddc: 610
    Language: German
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  • 5
    Publication Date: 2014-09-19
    Description: Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P 〈 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185210/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185210/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perry, John R B -- Day, Felix -- Elks, Cathy E -- Sulem, Patrick -- Thompson, Deborah J -- Ferreira, Teresa -- He, Chunyan -- Chasman, Daniel I -- Esko, Tonu -- Thorleifsson, Gudmar -- Albrecht, Eva -- Ang, Wei Q -- Corre, Tanguy -- Cousminer, Diana L -- Feenstra, Bjarke -- Franceschini, Nora -- Ganna, Andrea -- Johnson, Andrew D -- Kjellqvist, Sanela -- Lunetta, Kathryn L -- McMahon, George -- Nolte, Ilja M -- Paternoster, Lavinia -- Porcu, Eleonora -- Smith, Albert V -- Stolk, Lisette -- Teumer, Alexander -- Tsernikova, Natalia -- Tikkanen, Emmi -- Ulivi, Sheila -- Wagner, Erin K -- Amin, Najaf -- Bierut, Laura J -- Byrne, Enda M -- Hottenga, Jouke-Jan -- Koller, Daniel L -- Mangino, Massimo -- Pers, Tune H -- Yerges-Armstrong, Laura M -- Hua Zhao, Jing -- Andrulis, Irene L -- Anton-Culver, Hoda -- Atsma, Femke -- Bandinelli, Stefania -- Beckmann, Matthias W -- Benitez, Javier -- Blomqvist, Carl -- Bojesen, Stig E -- Bolla, Manjeet K -- Bonanni, Bernardo -- Brauch, Hiltrud -- Brenner, Hermann -- Buring, Julie E -- Chang-Claude, Jenny -- Chanock, Stephen -- Chen, Jinhui -- Chenevix-Trench, Georgia -- Collee, J Margriet -- Couch, Fergus J -- Couper, David -- Coviello, Andrea D -- Cox, Angela -- Czene, Kamila -- D'adamo, Adamo Pio -- Davey Smith, George -- De Vivo, Immaculata -- Demerath, Ellen W -- Dennis, Joe -- Devilee, Peter -- Dieffenbach, Aida K -- Dunning, Alison M -- Eiriksdottir, Gudny -- Eriksson, Johan G -- Fasching, Peter A -- Ferrucci, Luigi -- Flesch-Janys, Dieter -- Flyger, Henrik -- Foroud, Tatiana -- Franke, Lude -- Garcia, Melissa E -- Garcia-Closas, Montserrat -- Geller, Frank -- de Geus, Eco E J -- Giles, Graham G -- Gudbjartsson, Daniel F -- Gudnason, Vilmundur -- Guenel, Pascal -- Guo, Suiqun -- Hall, Per -- Hamann, Ute -- Haring, Robin -- Hartman, Catharina A -- Heath, Andrew C -- Hofman, Albert -- Hooning, Maartje J -- Hopper, John L -- Hu, Frank B -- Hunter, David J -- Karasik, David -- Kiel, Douglas P -- Knight, Julia A -- Kosma, Veli-Matti -- Kutalik, Zoltan -- Lai, Sandra -- Lambrechts, Diether -- Lindblom, Annika -- Magi, Reedik -- Magnusson, Patrik K -- Mannermaa, Arto -- Martin, Nicholas G -- Masson, Gisli -- McArdle, Patrick F -- McArdle, Wendy L -- Melbye, Mads -- Michailidou, Kyriaki -- Mihailov, Evelin -- Milani, Lili -- Milne, Roger L -- Nevanlinna, Heli -- Neven, Patrick -- Nohr, Ellen A -- Oldehinkel, Albertine J -- Oostra, Ben A -- Palotie, Aarno -- Peacock, Munro -- Pedersen, Nancy L -- Peterlongo, Paolo -- Peto, Julian -- Pharoah, Paul D P -- Postma, Dirkje S -- Pouta, Anneli -- Pylkas, Katri -- Radice, Paolo -- Ring, Susan -- Rivadeneira, Fernando -- Robino, Antonietta -- Rose, Lynda M -- Rudolph, Anja -- Salomaa, Veikko -- Sanna, Serena -- Schlessinger, David -- Schmidt, Marjanka K -- Southey, Mellissa C -- Sovio, Ulla -- Stampfer, Meir J -- Stockl, Doris -- Storniolo, Anna M -- Timpson, Nicholas J -- Tyrer, Jonathan -- Visser, Jenny A -- Vollenweider, Peter -- Volzke, Henry -- Waeber, Gerard -- Waldenberger, Melanie -- Wallaschofski, Henri -- Wang, Qin -- Willemsen, Gonneke -- Winqvist, Robert -- Wolffenbuttel, Bruce H R -- Wright, Margaret J -- Australian Ovarian Cancer Study -- GENICA Network -- kConFab -- LifeLines Cohort Study -- InterAct Consortium -- Early Growth Genetics (EGG) Consortium -- Boomsma, Dorret I -- Econs, Michael J -- Khaw, Kay-Tee -- Loos, Ruth J F -- McCarthy, Mark I -- Montgomery, Grant W -- Rice, John P -- Streeten, Elizabeth A -- Thorsteinsdottir, Unnur -- van Duijn, Cornelia M -- Alizadeh, Behrooz Z -- Bergmann, Sven -- Boerwinkle, Eric -- Boyd, Heather A -- Crisponi, Laura -- Gasparini, Paolo -- Gieger, Christian -- Harris, Tamara B -- Ingelsson, Erik -- Jarvelin, Marjo-Riitta -- Kraft, Peter -- Lawlor, Debbie -- Metspalu, Andres -- Pennell, Craig E -- Ridker, Paul M -- Snieder, Harold -- Sorensen, Thorkild I A -- Spector, Tim D -- Strachan, David P -- Uitterlinden, Andre G -- Wareham, Nicholas J -- Widen, Elisabeth -- Zygmunt, Marek -- Murray, Anna -- Easton, Douglas F -- Stefansson, Kari -- Murabito, Joanne M -- Ong, Ken K -- 098381/Wellcome Trust/United Kingdom -- 10118/Cancer Research UK/United Kingdom -- G0701863/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- G9815508/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106179472/Medical Research Council/United Kingdom -- MC_UU_12013/1/Medical Research Council/United Kingdom -- MC_UU_12013/3/Medical Research Council/United Kingdom -- MC_UU_12015/1/Medical Research Council/United Kingdom -- MC_UU_12015/2/Medical Research Council/United Kingdom -- MR/J012165/1/Medical Research Council/United Kingdom -- P50 CA116201/CA/NCI NIH HHS/ -- R01 AG041517/AG/NIA NIH HHS/ -- UL1 TR001108/TR/NCATS NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):92-7. doi: 10.1038/nature13545. Epub 2014 Jul 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. [3] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [4] Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. [5]. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2]. ; 1] deCODE Genetics, Reykjavik IS-101, Iceland. [2]. ; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; 1] Department of Epidemiology, Indiana University Richard M Fairbanks School of Public Health, Indianapolis, Indiana 46202, USA. [2] Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202, USA. ; 1] Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia. [2] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [3] Broad Institute of the Massachusetts Institute of Technology and Harvard University, 140 Cambridge, Massachusetts 02142, USA. [4] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; deCODE Genetics, Reykjavik IS-101, Iceland. ; Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-85764 Neuherberg, Germany. ; School of Women's and Infants' Health, The University of Western Australia, WA-6009, Australia. ; 1] Department of Medical Genetics, University of Lausanne, CH-1005 Lausanne, Switzerland. [2] Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland. ; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Finland. ; Department of Epidemiology Research, Statens Serum Institut, DK-2300 Copenhagen, Denmark. ; Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599-7400, USA. ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden. ; NHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA. ; Science for Life Laboratory, Karolinska Institutet, Stockholm, Box 1031, 17121 Solna, Sweden. ; 1] NHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA. [2] Boston University School of Public Health, Department of Biostatistics, Boston, Massachusetts 02118, USA. ; 1] MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. [2] School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. ; Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands. ; MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. ; 1] Institute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy. [2] University of Sassari, Department of Biomedical Sciences, 07100 Sassari, Italy. ; 1] Icelandic Heart Association, IS-201 Kopavogur, Iceland. [2] University of Iceland, IS-101 Reykjavik, Iceland. ; 1] Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, the Netherlands. [2] Netherlands Consortium on Health Aging and National Genomics Initiative, 2300 RC Leiden, the Netherlands. ; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17475 Greifswald, Germany. ; 1] Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia. [2] Department of Biotechnology, University of Tartu, 51010 Tartu, Estonia. ; 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Finland. [2] Hjelt Institute, University of Helsinki, FI-00014, Finland. ; Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy. ; Genetic Epidemiology Unit Department of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, the Netherlands. ; Department of Psychiatry, Washington University, St Louis, Missouri 63110, USA. ; 1] The University of Queensland, Queensland Brain Institute, St Lucia, Queensland 4072, Australia. [2] QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia. ; Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands. ; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202-3082, USA. ; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; 1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA. [2] Broad Institute of the Massachusetts Institute of Technology and Harvard University, 140 Cambridge, Massachusetts 02142, USA. [3] Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [4] Center for Biological Sequence Analysis, Department of Systems Biology, Technical 142 University of Denmark, DK-2800 Lyngby, Denmark. ; Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. ; 1] Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Epidemiology, University of California Irvine, Irvine, California 92697-7550, USA. ; Sanquin Research, 6525 GA Nijmegen, The Netherlands. ; 1] Tuscany Regional Health Agency, Florence, Italy, I.O.T. and Department of Medical and Surgical Critical Care, University of Florence, 50134 Florence, Italy. [2] Geriatric Unit, Azienda Sanitaria di Firenze, 50122 Florence, Italy. ; University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, D-91054 Erlangen, Germany. ; 1] Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), E-28029 Madrid, Spain. [2] Centro de Investigacion en Red de Enfermedades Raras (CIBERER), E-46010 Valencia, Spain. ; Department of Oncology, University of Helsinki and Helsinki University Central Hospital, FI-00100 Helsinki, Finland. ; 1] Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, DK-2100 Copenhagen, Denmark. [2] Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, DK-2100 Copenhagen, Denmark. ; Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), 20139 Milan, Italy. ; 1] DrMargarete Fischer-Bosch-Institute of Clinical Pharmacology, D-70376 Stuttgart, Germany. [2] University of Tubingen, D-72074 Tubingen, Germany. ; 1] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany. [2] German Cancer Consortium (DKTK), D-69120 Heidelberg, Germany. ; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. ; 1] Departments of Anatomy and Neurological Surgery, Indiana University school of Medicine, Indianapolis, Indiana 46202, USA. [2] Stark Neuroscience Research Center, Indiana University school of Medicine, Indianapolis, Indiana 46202, USA. ; Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006 Australia. ; Department of Clinical Genetics, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands. ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. ; Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina 27599-7420, USA. ; Boston University School of Medicine, Department of Medicine, Sections of Preventive Medicine and Endocrinology, Boston, Massachusetts 02118, USA. ; Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield S10 2RX, UK. ; 1] Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", 34137 Trieste, Italy. [2] Department of Clinical Medical Sciences, Surgical and Health, University of Trieste, 34149 Trieste, Italy. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota 55455, USA. ; Department of Human Genetics &Department of Pathology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge CB1 8RN, UK. ; Icelandic Heart Association, IS-201 Kopavogur, Iceland. ; 1] National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland. [2] Department of General Practice and Primary health Care, University of Helsinki, FI-00014 Helsinki, Finland. [3] Helsinki University Central Hospital, Unit of General Practice, FI-00029 HUS Helsinki, Finland. [4] Folkhalsan Research Centre, FI-00290 Helsinki, Finland. ; Longitudinal Studies Section, Clinical Research Branch, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland 20892, USA. ; Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, D-20246 Hamburg, Germany. ; Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark. ; Department of Genetics, University of Groningen, University Medical Centre Groningen, P.O. Box 72, 9700 AB Groningen, The Netherlands. ; National Insitute on Aging, National Institutes of Health, Baltimore, Maryland 20892, USA. ; 1] Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. [2] Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research, London SW3 6JB, UK. ; 1] Department of Biological Psychology, VU University Amsterdam, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands. [2] EMGO + Institute for Health and Care Research, VU University Medical Centre, Van der Boechorststraat 7, 1081 Bt, Amsterdam, The Netherlands. ; 1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia. ; 1] deCODE Genetics, Reykjavik IS-101, Iceland. [2] Faculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland. ; 1] Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, F-94807 Villejuif, France. [2] University Paris-Sud, UMRS 1018, F-94807 Villejuif, France. ; Department of Obstetrics and Gynecology, Southern Medical University, 510515 Guangzhou, China. ; Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg, Germany. ; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. ; Department of Psychiatry, University of Groningen, University Medical Center Groningen, P.O. Box 72, 9700 AB Groningen, The Netherlands. ; Washington University, Department of Psychiatry, St Louis, Missouri 63110, USA. ; Department of Epidemiology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, the Netherlands. ; Department of Medical Oncology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. ; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; 1] Broad Institute of the Massachusetts Institute of Technology and Harvard University, 140 Cambridge, Massachusetts 02142, USA. [2] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [3] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Hebrew SeniorLife Institute for Aging Research, Boston, Massachusetts 02131, USA. ; 1] Hebrew SeniorLife Institute for Aging Research, Boston, Massachusetts 02131, USA. [2] Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. [2] Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario M5T 3M7, Canada. ; 1] School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland. [2] Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, P.O. Box 100, FI-70029 Kuopio, Finland. ; Institute of Genetics and Biomedical Research, National Research Council, Cagliari, 09042 Sardinia, Italy. ; 1] Vesalius Research Center (VRC), VIB, 3000 Leuven, Belgium. [2] Laboratory for Translational Genetics, Department of Oncology, University of Leuven, 3000 Leuven, Belgium. ; Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden. ; Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia. ; School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. ; 1] Department of Epidemiology Research, Statens Serum Institut, DK-2300 Copenhagen, Denmark. [2] Department of Medicine, Stanford School of Medicine, Stanford, California 94305-5101, USA. ; Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, P.O. Box 100, FI-00029 HUS Helsinki, Finland. ; KULeuven (University of Leuven), Department of Oncology, Multidisciplinary Breast Center, University Hospitals Leuven, 3000 Leuven, Belgium. ; Research Unit of Obstetrics &Gynecology, Institute of Clinical Research, University of Southern Denmark, DK-5000 Odense C, Denmark. ; Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. ; 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FI-00014, Finland. [2] Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [4] Psychiatric &Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy. ; Non-communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK. ; University Groningen, University Medical Center Groningen, Department Pulmonary Medicine and Tuberculosis, GRIAC Research Institute, P.O. Box 30.001, NL-9700 RB Groningen, The Netherlands. ; 1] National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland. [2] Department of Obstetrics and Gynecology, Oulu University Hospital, P.O. Box 10, FI-90029 OYS Oulu, Finland. ; Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, Oulu University Hospital/NordLab Oulu, P.O. Box 3000, FI-90014 Oulu, Finland. ; Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133 Milan, Italy. ; 1] Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, the Netherlands. [2] Netherlands Consortium on Health Aging and National Genomics Initiative, 2300 RC Leiden, the Netherlands. [3] Department of Epidemiology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, the Netherlands. ; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. ; National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland. ; National Institute on Aging, Intramural Research Program, Baltimore, Maryland 21224-6825, USA. ; Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Postbus 90203, 1006 BE Amsterdam, The Netherlands. ; Department of Pathology, The University of Melbourne, Melbourne, Victoria 3010, Australia. ; 1] Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK. [2] Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge CB2 0SW, UK. ; 1] Institute of Epidemiology II, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-8576 Neuherberg, Germany. [2] Department of Obstetrics and Gynaecology, Campus Grosshadern, Ludwig-Maximilians-University, D-81377 Munich, Germany. ; Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, the Netherlands. ; Department of Internal Medicine, Lausanne University Hospital, CH-1015 Lausanne, Switzerland. ; 1] Institute for Community Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, D-8576 Neuherberg, Germany. ; 1] Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany. [2] DZHK (German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany. ; Department of Endocrinology, University of Groningen, University Medical Centre Groningen, P.O. Box 72, 9700 AB Groningen, The Netherlands. ; Queensland Insitute of Medical Research, Brisbane, Queensland 4029, Australia. ; 1] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202-3082, USA. [2] Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 0QQ, UK. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute for Personalized Medicine, The Mindich Child Health and Development Institute, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, Box 1003, New York, New York 10029, USA. ; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [2] NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford OX3 7LE, UK. [3] Oxford Centre for Diabetes, Endocrinology, &Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK. ; 1] Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [2] Geriatric Research and Education Clinical Center (GRECC) - Veterans Administration Medical Center, Baltimore, Maryland 21201, USA. ; 1] Netherlands Consortium on Health Aging and National Genomics Initiative, 2300 RC Leiden, the Netherlands. [2] Genetic Epidemiology Unit Department of Epidemiology, Erasmus MC, 3015 GE, Rotterdam, the Netherlands. [3] Centre of Medical Systems Biology, PO Box 9600, 2300 RC Leiden, the Netherlands. ; Human Genetics Center and Divof Epidemiology, University of Houston, P.O. Box 20186, Texas 77025 USA. ; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Box 256, 751 05 Uppsala, Sweden. ; 1] Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK. [2] Institute of Health Sciences, University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland. [3] Biocenter Oulu, University of Oulu, P.O. Box 5000, Aapistie 5A, FI-90014 Oulu, Finland. [4] Department of Children and Young People and Families, National Institute for Health and Welfare, Aapistie 1, Box 310, FI-90101 Oulu, Finland. [5] Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O. Box 20, FI-90220 Oulu, 90029 OYS, Finland. ; 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ; 1] Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200, Denmark. [2] Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, DK-2000 Frederiksberg, Denmark. ; Division of Population Health Sciences and Education, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK. ; Department of Obstetrics and Gynecology, University Medicine Greifswald, D-17475 Greifswald, Germany. ; University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK. ; 1] deCODE Genetics, Reykjavik IS-101, Iceland. [2] Faculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland. [3]. ; 1] NHLBI's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA. [2] Boston University School of Medicine, Department of Medicine, Section of General Internal Medicine, Boston, Massachusetts 02118, USA. [3]. ; 1] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Department of Paediatrics, University of Cambridge, Cambridge CB2 0QQ, UK. [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25231870" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Age Factors ; *Alleles ; Body Mass Index ; Breast Neoplasms/genetics ; Cardiovascular Diseases/genetics ; Child ; Diabetes Mellitus, Type 2/genetics ; Europe/ethnology ; Female ; Genetic Loci/*genetics ; Genome-Wide Association Study ; Genomic Imprinting/genetics ; Humans ; Hypothalamo-Hypophyseal System/physiology ; Intercellular Signaling Peptides and Proteins/genetics ; Male ; Membrane Proteins/genetics ; Menarche/*genetics ; Obesity/genetics ; Ovary/physiology ; *Parents ; Polymorphism, Single Nucleotide/genetics ; Potassium Channels, Tandem Pore Domain/genetics ; Proteins/genetics ; Quantitative Trait Loci/genetics ; Receptors, GABA-B/metabolism ; Receptors, Retinoic Acid/metabolism ; Ribonucleoproteins/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2014-07-06
    Description: The large spectrum of limb morphologies reflects the wide evolutionary diversification of the basic pentadactyl pattern in tetrapods. In even-toed ungulates (artiodactyls, including cattle), limbs are adapted for running as a consequence of progressive reduction of their distal skeleton to symmetrical and elongated middle digits with hoofed phalanges. Here we analyse bovine embryos to establish that polarized gene expression is progressively lost during limb development in comparison to the mouse. Notably, the transcriptional upregulation of the Ptch1 gene, which encodes a Sonic hedgehog (SHH) receptor, is disrupted specifically in the bovine limb bud mesenchyme. This is due to evolutionary alteration of a Ptch1 cis-regulatory module, which no longer responds to graded SHH signalling during bovine handplate development. Our study provides a molecular explanation for the loss of digit asymmetry in bovine limb buds and suggests that modifications affecting the Ptch1 cis-regulatory landscape have contributed to evolutionary diversification of artiodactyl limbs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lopez-Rios, Javier -- Duchesne, Amandine -- Speziale, Dario -- Andrey, Guillaume -- Peterson, Kevin A -- Germann, Philipp -- Unal, Erkan -- Liu, Jing -- Floriot, Sandrine -- Barbey, Sarah -- Gallard, Yves -- Muller-Gerbl, Magdalena -- Courtney, Andrew D -- Klopp, Christophe -- Rodriguez, Sabrina -- Ivanek, Robert -- Beisel, Christian -- Wicking, Carol -- Iber, Dagmar -- Robert, Benoit -- McMahon, Andrew P -- Duboule, Denis -- Zeller, Rolf -- NS 033642/NS/NINDS NIH HHS/ -- England -- Nature. 2014 Jul 3;511(7507):46-51. doi: 10.1038/nature13289. Epub 2014 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2]. ; 1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Institut National de la Recherche Agronomique, Genetique Animale et Biologie Integrative, F-78350 Jouy-en-Josas, France [3]. ; Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland. ; School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland. ; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA. ; Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland. ; 1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland. ; Institut National de la Recherche Agronomique, Genetique Animale et Biologie Integrative, F-78350 Jouy-en-Josas, France. ; Institut National de la Recherche Agronomique, Domaine Experimental du Pin au Haras, F-61310 Exmes, France. ; Institute of Anatomy, Department Biomedicine, University of Basel, CH-4056 Basel, Switzerland. ; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia. ; Institut National de la Recherche Agronomique, Biometrie et Intelligence Artificielle, F-31326 Castanet-Tolosan, France. ; 1] Institut National de la Recherche Agronomique, Genetique Animale et Biologie Integrative, F-78350 Jouy-en-Josas, France [2] Institut National de la Recherche Agronomique, Laboratoire d'Ingenierie des Systemes Biologiques et des Procedes, F-31077 Toulouse, France. ; 1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland. ; Institut Pasteur, Genetique Moleculaire de la Morphogenese and Centre National de la Recherche Scientifique URA-2578, F-75015 Paris, France. ; 1] School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland [2] Department of Genetics and Evolution, University of Geneva, CH-1211 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24990743" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Body Patterning ; Cattle ; Extremities/*anatomy & histology/*embryology ; Female ; Gene Expression Regulation, Developmental/genetics ; Hedgehog Proteins/*metabolism ; Limb Buds/anatomy & histology/embryology ; Male ; Mesoderm/metabolism ; Mice ; Mice, Transgenic ; Receptors, Cell Surface/genetics/*metabolism ; Regulatory Sequences, Nucleic Acid/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2014-12-18
    Description: During endocytosis, energy is invested to narrow the necks of cargo-containing plasma membrane invaginations to radii at which the opposing segments spontaneously coalesce, thereby leading to the detachment by scission of endocytic uptake carriers. In the clathrin pathway, dynamin uses mechanical energy from GTP hydrolysis to this effect, assisted by the BIN/amphiphysin/Rvs (BAR) domain-containing protein endophilin. Clathrin-independent endocytic events are often less reliant on dynamin, and whether in these cases BAR domain proteins such as endophilin contribute to scission has remained unexplored. Here we show, in human and other mammalian cell lines, that endophilin-A2 (endoA2) specifically and functionally associates with very early uptake structures that are induced by the bacterial Shiga and cholera toxins, which are both clathrin-independent endocytic cargoes. In controlled in vitro systems, endoA2 reshapes membranes before scission. Furthermore, we demonstrate that endoA2, dynamin and actin contribute in parallel to the scission of Shiga-toxin-induced tubules. Our results establish a novel function of endoA2 in clathrin-independent endocytosis. They document that distinct scission factors operate in an additive manner, and predict that specificity within a given uptake process arises from defined combinations of universal modules. Our findings highlight a previously unnoticed link between membrane scaffolding by endoA2 and pulling-force-driven dynamic scission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342003/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342003/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Renard, Henri-Francois -- Simunovic, Mijo -- Lemiere, Joel -- Boucrot, Emmanuel -- Garcia-Castillo, Maria Daniela -- Arumugam, Senthil -- Chambon, Valerie -- Lamaze, Christophe -- Wunder, Christian -- Kenworthy, Anne K -- Schmidt, Anne A -- McMahon, Harvey T -- Sykes, Cecile -- Bassereau, Patricia -- Johannes, Ludger -- R01 GM106720/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Jan 22;517(7535):493-6. doi: 10.1038/nature14064. Epub 2014 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institut Curie - Centre de Recherche, Endocytic Trafficking and Therapeutic Delivery group, 26 rue d'Ulm, 75248 Paris Cedex 05, France [2] CNRS UMR3666, 75005 Paris, France [3] U1143 INSERM, 75005 Paris, France. ; 1] Institut Curie - Centre de Recherche, Membrane and Cell Functions group, CNRS UMR 168, Physico-Chimie Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France [2] The University of Chicago, Department of Chemistry, 5735 S Ellis Ave, Chicago, Ilinois 60637, USA. ; 1] Institut Curie - Centre de Recherche, Biomimetism of Cell Movement group, CNRS UMR 168, Physico-Chimie Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France [2] Universite Paris Diderot, Sorbonne Paris Cite, 75205 Paris, France. ; Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; 1] CNRS UMR3666, 75005 Paris, France [2] U1143 INSERM, 75005 Paris, France [3] Institut Curie - Centre de Recherche, Membrane Dynamics and Mechanics of Intracellular Signaling group, 26 rue d'Ulm, 75248 Paris Cedex 05, France. ; Vanderbilt School of Medicine, Department of Molecular Physiology and Biophysics, 718 Light Hall, Nashville, Tennessee 37232, USA. ; CNRS, UMR7592, Institut Jacques Monod, Universite Paris Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris Cedex 13, France. ; Medical Research Council, Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; Institut Curie - Centre de Recherche, Biomimetism of Cell Movement group, CNRS UMR 168, Physico-Chimie Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France. ; Institut Curie - Centre de Recherche, Membrane and Cell Functions group, CNRS UMR 168, Physico-Chimie Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517096" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Acyltransferases/*metabolism ; Animals ; Cell Line ; Cell Membrane/*metabolism ; Cholera Toxin/metabolism ; Clathrin ; Dynamins/metabolism ; *Endocytosis ; Humans ; Rats ; Shiga Toxin/metabolism
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2014-12-18
    Description: Endocytosis is required for internalization of micronutrients and turnover of membrane components. Endophilin has been assigned as a component of clathrin-mediated endocytosis. Here we show in mammalian cells that endophilin marks and controls a fast-acting tubulovesicular endocytic pathway that is independent of AP2 and clathrin, activated upon ligand binding to cargo receptors, inhibited by inhibitors of dynamin, Rac, phosphatidylinositol-3-OH kinase, PAK1 and actin polymerization, and activated upon Cdc42 inhibition. This pathway is prominent at the leading edges of cells where phosphatidylinositol-3,4-bisphosphate-produced by the dephosphorylation of phosphatidylinositol-3,4,5-triphosphate by SHIP1 and SHIP2-recruits lamellipodin, which in turn engages endophilin. This pathway mediates the ligand-triggered uptake of several G-protein-coupled receptors such as alpha2a- and beta1-adrenergic, dopaminergic D3 and D4 receptors and muscarinic acetylcholine receptor 4, the receptor tyrosine kinases EGFR, HGFR, VEGFR, PDGFR, NGFR and IGF1R, as well as interleukin-2 receptor. We call this new endocytic route fast endophilin-mediated endocytosis (FEME).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boucrot, Emmanuel -- Ferreira, Antonio P A -- Almeida-Souza, Leonardo -- Debard, Sylvain -- Vallis, Yvonne -- Howard, Gillian -- Bertot, Laetitia -- Sauvonnet, Nathalie -- McMahon, Harvey T -- U105178805/Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2015 Jan 22;517(7535):460-5. doi: 10.1038/nature14067. Epub 2014 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK [2] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; 1] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK [2] Department of Biology, Ecole Normale Superieure de Cachan, 94235 Cachan, France. ; Institut Pasteur, Unite de Pathogenie Moleculaire Microbienne, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517094" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Acyltransferases/*metabolism ; Cell Line ; Clathrin ; Dynamins/metabolism ; *Endocytosis ; Humans ; Ligands ; Phosphatidylinositol Phosphates/metabolism ; Pseudopodia/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Interleukin-2/metabolism ; Signal Transduction ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2016-05-27
    Description: Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okbay, Aysu -- Beauchamp, Jonathan P -- Fontana, Mark Alan -- Lee, James J -- Pers, Tune H -- Rietveld, Cornelius A -- Turley, Patrick -- Chen, Guo-Bo -- Emilsson, Valur -- Meddens, S Fleur W -- Oskarsson, Sven -- Pickrell, Joseph K -- Thom, Kevin -- Timshel, Pascal -- de Vlaming, Ronald -- Abdellaoui, Abdel -- Ahluwalia, Tarunveer S -- Bacelis, Jonas -- Baumbach, Clemens -- Bjornsdottir, Gyda -- Brandsma, Johannes H -- Pina Concas, Maria -- Derringer, Jaime -- Furlotte, Nicholas A -- Galesloot, Tessel E -- Girotto, Giorgia -- Gupta, Richa -- Hall, Leanne M -- Harris, Sarah E -- Hofer, Edith -- Horikoshi, Momoko -- Huffman, Jennifer E -- Kaasik, Kadri -- Kalafati, Ioanna P -- Karlsson, Robert -- Kong, Augustine -- Lahti, Jari -- van der Lee, Sven J -- deLeeuw, Christiaan -- Lind, Penelope A -- Lindgren, Karl-Oskar -- Liu, Tian -- Mangino, Massimo -- Marten, Jonathan -- Mihailov, Evelin -- Miller, Michael B -- van der Most, Peter J -- Oldmeadow, Christopher -- Payton, Antony -- Pervjakova, Natalia -- Peyrot, Wouter J -- Qian, Yong -- Raitakari, Olli -- Rueedi, Rico -- Salvi, Erika -- Schmidt, Borge -- Schraut, Katharina E -- Shi, Jianxin -- Smith, Albert V -- Poot, Raymond A -- St Pourcain, Beate -- Teumer, Alexander -- Thorleifsson, Gudmar -- Verweij, Niek -- Vuckovic, Dragana -- Wellmann, Juergen -- Westra, Harm-Jan -- Yang, Jingyun -- Zhao, Wei -- Zhu, Zhihong -- Alizadeh, Behrooz Z -- Amin, Najaf -- Bakshi, Andrew -- Baumeister, Sebastian E -- Biino, Ginevra -- Bonnelykke, Klaus -- Boyle, Patricia A -- Campbell, Harry -- Cappuccio, Francesco P -- Davies, Gail -- De Neve, Jan-Emmanuel -- Deloukas, Panos -- Demuth, Ilja -- Ding, Jun -- Eibich, Peter -- Eisele, Lewin -- Eklund, Niina -- Evans, David M -- Faul, Jessica D -- Feitosa, Mary F -- Forstner, Andreas J -- Gandin, Ilaria -- Gunnarsson, Bjarni -- Halldorsson, Bjarni V -- Harris, Tamara B -- Heath, Andrew C -- Hocking, Lynne J -- Holliday, Elizabeth G -- Homuth, Georg -- Horan, Michael A -- Hottenga, Jouke-Jan -- de Jager, Philip L -- Joshi, Peter K -- Jugessur, Astanand -- Kaakinen, Marika A -- Kahonen, Mika -- Kanoni, Stavroula -- Keltigangas-Jarvinen, Liisa -- Kiemeney, Lambertus A L M -- Kolcic, Ivana -- Koskinen, Seppo -- Kraja, Aldi T -- Kroh, Martin -- Kutalik, Zoltan -- Latvala, Antti -- Launer, Lenore J -- Lebreton, Mael P -- Levinson, Douglas F -- Lichtenstein, Paul -- Lichtner, Peter -- Liewald, David C M -- LifeLines Cohort Study -- Loukola, Anu -- Madden, Pamela A -- Magi, Reedik -- Maki-Opas, Tomi -- Marioni, Riccardo E -- Marques-Vidal, Pedro -- Meddens, Gerardus A -- McMahon, George -- Meisinger, Christa -- Meitinger, Thomas -- Milaneschi, Yusplitri -- Milani, Lili -- Montgomery, Grant W -- Myhre, Ronny -- Nelson, Christopher P -- Nyholt, Dale R -- Ollier, William E R -- Palotie, Aarno -- Paternoster, Lavinia -- Pedersen, Nancy L -- Petrovic, Katja E -- Porteous, David J -- Raikkonen, Katri -- Ring, Susan M -- Robino, Antonietta -- Rostapshova, Olga -- Rudan, Igor -- Rustichini, Aldo -- Salomaa, Veikko -- Sanders, Alan R -- Sarin, Antti-Pekka -- Schmidt, Helena -- Scott, Rodney J -- Smith, Blair H -- Smith, Jennifer A -- Staessen, Jan A -- Steinhagen-Thiessen, Elisabeth -- Strauch, Konstantin -- Terracciano, Antonio -- Tobin, Martin D -- Ulivi, Sheila -- Vaccargiu, Simona -- Quaye, Lydia -- van Rooij, Frank J A -- Venturini, Cristina -- Vinkhuyzen, Anna A E -- Volker, Uwe -- Volzke, Henry -- Vonk, Judith M -- Vozzi, Diego -- Waage, Johannes -- Ware, Erin B -- Willemsen, Gonneke -- Attia, John R -- Bennett, David A -- Berger, Klaus -- Bertram, Lars -- Bisgaard, Hans -- Boomsma, Dorret I -- Borecki, Ingrid B -- Bultmann, Ute -- Chabris, Christopher F -- Cucca, Francesco -- Cusi, Daniele -- Deary, Ian J -- Dedoussis, George V -- van Duijn, Cornelia M -- Eriksson, Johan G -- Franke, Barbara -- Franke, Lude -- Gasparini, Paolo -- Gejman, Pablo V -- Gieger, Christian -- Grabe, Hans-Jorgen -- Gratten, Jacob -- Groenen, Patrick J F -- Gudnason, Vilmundur -- van der Harst, Pim -- Hayward, Caroline -- Hinds, David A -- Hoffmann, Wolfgang -- Hypponen, Elina -- Iacono, William G -- Jacobsson, Bo -- Jarvelin, Marjo-Riitta -- Jockel, Karl-Heinz -- Kaprio, Jaakko -- Kardia, Sharon L R -- Lehtimaki, Terho -- Lehrer, Steven F -- Magnusson, Patrik K E -- Martin, Nicholas G -- McGue, Matt -- Metspalu, Andres -- Pendleton, Neil -- Penninx, Brenda W J H -- Perola, Markus -- Pirastu, Nicola -- Pirastu, Mario -- Polasek, Ozren -- Posthuma, Danielle -- Power, Christine -- Province, Michael A -- Samani, Nilesh J -- Schlessinger, David -- Schmidt, Reinhold -- Sorensen, Thorkild I A -- Spector, Tim D -- Stefansson, Kari -- Thorsteinsdottir, Unnur -- Thurik, A Roy -- Timpson, Nicholas J -- Tiemeier, Henning -- Tung, Joyce Y -- Uitterlinden, Andre G -- Vitart, Veronique -- Vollenweider, Peter -- Weir, David R -- Wilson, James F -- Wright, Alan F -- Conley, Dalton C -- Krueger, Robert F -- Davey Smith, George -- Hofman, Albert -- Laibson, David I -- Medland, Sarah E -- Meyer, Michelle N -- Yang, Jian -- Johannesson, Magnus -- Visscher, Peter M -- Esko, Tonu -- Koellinger, Philipp D -- Cesarini, David -- Benjamin, Daniel J -- P01-AG005842/AG/NIA NIH HHS/ -- P01-AG005842-20S2/AG/NIA NIH HHS/ -- P30-AG012810/AG/NIA NIH HHS/ -- R01-AG042568/AG/NIA NIH HHS/ -- T32-AG000186-23/AG/NIA NIH HHS/ -- England -- Nature. 2016 May 11;533(7604):539-42. doi: 10.1038/nature17671.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, 3062 PA, The Netherlands. ; Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands. ; Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, 3062 PA, The Netherlands. ; Department of Economics, Harvard University, Cambridge, Massachusetts 02138, USA. ; Center for Economic and Social Research, University of Southern California, Los Angeles, California 90089-3332, USA. ; Department of Psychology, University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, USA. ; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 2116, USA. ; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen 2100, Denmark. ; Statens Serum Institut, Department of Epidemiology Research, Copenhagen 2300, Denmark. ; Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. ; Icelandic Heart Association, Kopavogur 201, Iceland. ; Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik 107, Iceland. ; Department of Complex Trait Genetics, VU University, Center for Neurogenomics and Cognitive Research, Amsterdam, 1081 HV, The Netherlands. ; Amsterdam Business School, University of Amsterdam, Amsterdam, 1018 TV, The Netherlands. ; Department of Government, Uppsala University, Uppsala 751 20, Sweden. ; New York Genome Center, New York, New York 10013, USA. ; Department of Economics, New York University, New York, New York 10012, USA. ; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark Lyngby 2800, Denmark. ; Department of Biological Psychology, VU University Amsterdam, Amsterdam, 1081 BT, The Netherlands. ; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen 2820, Denmark. ; Steno Diabetes Center, Gentofte 2820, Denmark. ; Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg 416 85, Sweden. ; Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg 85764, Germany. ; Institute of Epidemiology II, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg 85764, Germany. ; deCODE Genetics/Amgen Inc., Reykjavik 101, Iceland. ; Department of Cell Biology, Erasmus Medical Center Rotterdam, 3015 CN, The Netherlands. ; Istituto di Ricerca Genetica e Biomedica U.O.S. di Sassari, National Research Council of Italy, Sassari 07100, Italy. ; Psychology, University of Illinois, Champaign, Illinois 61820, USA. ; 23andMe, Inc., Mountain View, California 94041, USA. ; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands. ; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34100, Italy. ; Department of Public Health, University of Helsinki, 00014 Helsinki, Finland. ; Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK. ; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK. ; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK. ; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Department of Neurology, General Hospital and Medical University Graz, Graz 8036, Austria. ; Institute for Medical Informatics, Statistics and Documentation, General Hospital and Medical University Graz, Graz 8036, Austria. ; Oxford Centre for Diabetes, Endocrinology &Metabolism, University of Oxford, Oxford OX3 7LE, UK. ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Institute of Behavioural Sciences, University of Helsinki, 00014 Helsinki, Finland. ; Nutrition and Dietetics, Health Science and Education, Harokopio University, Athens 17671, Greece. ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden. ; Folkhalsan Research Centre, 00014 Helsingfors, Finland. ; Institute for Computing and Information Sciences, Radboud University Nijmegen, Nijmegen, 6525 EC, The Netherlands. ; Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. ; Lifespan Psychology, Max Planck Institute for Human Development, Berlin 14195, Germany. ; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; NIHR Biomedical Research Centre, Guy's and St. Thomas' Foundation Trust, London SE1 7EH, UK. ; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. ; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands. ; Public Health Stream, Hunter Medical Research Institute, New Lambton, NSW 2305, Australia. ; Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW 2300, Australia. ; Centre for Integrated Genomic Medical Research, Institute of Population Health, The University of Manchester, Manchester M13 9PT, UK. ; Human Communication and Deafness, School of Psychological Sciences, The University of Manchester, Manchester M13 9PL, UK. ; Department of Health, THL-National Institute for Health and Welfare, 00271 Helsinki, Finland. ; Psychiatry, VU University Medical Center &GGZ inGeest, Amsterdam, 1081 HL, The Netherlands. ; Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland 21224, USA. ; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20521 Turku, Finland. ; Department of Medical Genetics, University of Lausanne, Lausanne 1005, Switzerland. ; Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland. ; Department Of Health Sciences, University of Milan, Milano 20142, Italy. ; Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen 45147, Germany. ; Centre for Global Health Research, The Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-9780, USA. ; Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland. ; MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. ; School of Oral and Dental Sciences, University of Bristol, Bristol BS1 2LY, UK. ; Institute for Community Medicine, University Medicine Greifswald, Greifswald 17475, Germany. ; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands. ; Institute of Epidemiology and Social Medicine, University of Munster, Munster 48149, Germany. ; Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Partners Center for Personalized Genetic Medicine, Boston, Massachusetts 02115, USA. ; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois 60612, USA. ; Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA. ; Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands. ; Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg D-93053, Germany. ; Institute of Molecular Genetics, National Research Council of Italy, Pavia 27100, Italy. ; Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA. ; Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK. ; Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. ; Said Business School, University of Oxford, Oxford OX1 1HP, UK. ; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah 21589, Saudi Arabia. ; The Berlin Aging Study II; Research Group on Geriatrics, Charite - Universitatsmedizin Berlin, Germany, Berlin 13347, Germany. ; Institute of Medical and Human Genetics, Charite-Universitatsmedizin, Berlin, Berlin 13353, Germany. ; German Socio- Economic Panel Study, DIW Berlin, Berlin 10117, Germany. ; Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK. ; The University of Queensland Diamantina Institute, The Translational Research Institute, Brisbane, QLD 4102, Australia. ; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri 63018, USA. ; Institute of Human Genetics, University of Bonn, Bonn 53127, Germany. ; Department of Genomics, Life and Brain Center, University of Bonn, Bonn 53127, Germany. ; Institute of Biomedical and Neural Engineering, School of Science and Engineering, Reykjavik University, Reykjavik 101, Iceland. ; Laboratory of Epidemiology, Demography, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892-9205, USA. ; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. ; Division of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK. ; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17475, Germany. ; Manchester Medical School, The University of Manchester, Manchester M13 9PT, UK. ; Program in Translational NeuroPsychiatric Genomics, Departments of Neurology &Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ; Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Genes and Environment, Norwegian Institute of Public Health, N-0403 Oslo, Norway. ; Department of Genomics of Common Disease, Imperial College London, London, W12 0NN, UK. ; Department of Clinical Physiology, Tampere University Hospital, 33521 Tampere, Finland. ; Department of Clinical Physiology, University of Tampere, School of Medicine, 33014 Tampere, Finland. ; Public Health, Medical School, University of Split, 21000 Split, Croatia. ; Institute of Social and Preventive Medicine, Lausanne University Hospital (CHUV), Lausanne 1010, Switzerland. ; Neuroepidemiology Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892-9205, USA. ; Amsterdam Brain and Cognition Center, University of Amsterdam, Amsterdam, 1018 XA, The Netherlands. ; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305-5797, USA. ; Institute of Human Genetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg 85764, Germany. ; Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK. ; Department of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne 1011, Switzerland. ; Tema BV, Hoofddorp, 2131 HE, The Netherlands. ; Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. ; Institute of Health and Biomedical Innovation, Queensland Institute of Technology, Brisbane, QLD 4059, Australia. ; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; Psychiatric &Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland. ; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Medical Genetics, Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste 34100, Italy. ; Social Impact, Arlington, Virginia 22201, USA. ; Department of Economics, University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, USA. ; Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, Illinois 60201-3137, USA. ; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois 60637, USA. ; Public Health Genomics Unit, National Institute for Health and Welfare, 00300 Helsinki, Finland. ; Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, General Hospital and Medical University, Graz, Graz 8010, Austria. ; Information Based Medicine Stream, Hunter Medical Research Institute, New Lambton, NSW 2305, Australia. ; Medical Research Institute, University of Dundee, Dundee DD1 9SY, UK. ; Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Science, University of Leuven, Leuven 3000, Belgium. ; R&D VitaK Group, Maastricht University, Maastricht, 6229 EV, The Netherlands. ; Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg 85764, Germany. ; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig Maximilians-Universitat, Munich 81377, Germany. ; Department of Geriatrics, Florida State University College of Medicine, Tallahassee, Florida 32306, USA. ; Department of Health Sciences and Genetics, University of Leicester, Leicester LE1 7RH, UK. ; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands. ; Research Center for Group Dynamics, Institute for Social Research, University of Michigan, Ann Arbor, Michigan 48104, USA. ; Platform for Genome Analytics, Institutes of Neurogenetics &Integrative and Experimental Genomics, University of Lubeck, Lubeck 23562, Germany. ; Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK. ; Department of Health Sciences, Community &Occupational Medicine, University of Groningen, University Medical Center Groningen, Groningen, 9713 AV, The Netherlands. ; Department of Psychology, Union College, Schenectady, New York 12308, USA. ; Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari 9042, Italy. ; Institute of Biomedical Technologies, Italian National Research Council, Segrate (Milano) 20090, Italy. ; Department of General Practice and Primary Health Care, University of Helsinki, 00014 Helsinki, Finland. ; Departments of Human Genetics and Psychiatry, Donders Centre for Neuroscience, Nijmegen, 6500 HB, The Netherlands. ; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands. ; Sidra, Experimental Genetics Division, Sidra, Doha 26999, Qatar. ; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald 17475, Germany. ; Department of Psychiatry and Psychotherapy, HELIOS-Hospital Stralsund, Stralsund 18437, Germany. ; Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, 3062 PA, The Netherlands. ; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, 1105 AZ, The Netherlands. ; Generation Scotland, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Centre for Population Health Research, School of Health Sciences and Sansom Institute, University of South Australia, Adelaide, SA 5000, Australia. ; South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia. ; Population, Policy and Practice, UCL Institute of Child Health, London WC1N 1EH, UK. ; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment &Health, School of Public Health, Imperial College London, London W2 1PG, UK. ; Center for Life Course Epidemiology, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland. ; Unit of Primary Care, Oulu University Hospital, 90029 Oulu, Finland. ; Biocenter Oulu, University of Oulu, 90014 Oulu, Finland. ; Fimlab Laboratories, 33520 Tampere, Finland. ; Department of Clinical Chemistry, University of Tampere, School of Medicine, 33014 Tampere, Finland. ; Economics, NYU Shanghai, 200122 Pudong, China. ; Policy Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada. ; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. ; Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia. ; Centre for Clinical and Cognitive Neuroscience, Institute Brain Behaviour and Mental Health, Salford Royal Hospital, Manchester M6 8HD, UK. ; Manchester Institute for Collaborative Research in Ageing, University of Manchester, Manchester M13 9PL, UK. ; Faculty of Medicine, University of Split, Split 21000, Croatia. ; Department of Clinical Genetics, VU Medical Centre, Amsterdam, 1081 HV, The Netherlands. ; Institute of Preventive Medicine. Bispebjerg and Frederiksberg Hospitals, The Capital Region, Frederiksberg 2000, Denmark. ; Montpellier Business School, Montpellier 34080, France. ; Panteia, Zoetermeer, 2715 CA, The Netherlands. ; Department of Psychiatry, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands. ; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands. ; Department of Sociology, New York University, New York, New York 10012, USA. ; School of Medicine, New York University, New York, New York 10016, USA. ; Bioethics Program, Union Graduate College - Icahn School of Medicine at Mount Sinai, Schenectady, New York 12308, USA. ; Department of Economics, Stockholm School of Economics, Stockholm 113 83, Sweden. ; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Research Institute for Industrial Economics, Stockholm 10215, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27225129" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    Nature Publishing Group (NPG)
    Publication Date: 2018-10-30
    Description: Linking brain tumors and epileptic seizures Linking brain tumors and epileptic seizures, Published online: 29 October 2018; doi:10.1038/s41591-018-0249-6 Mutationally activated BRAF-V600E influences the behavior of different types of cells in the brain and leads to promotion of seizures as well as brain tumors, indicating how both can be pharmacologically targeted in the clinic.
    Print ISSN: 1078-8956
    Electronic ISSN: 1546-170X
    Topics: Biology , Medicine
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