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Genetic variants for head size share genes and pathways with cancer

View ORCID ProfileMaria J. Knol, Raymond A. Poot, Tavia E. Evans, Claudia L. Satizabal, Aniket Mishra, Sandra van der Auwera, Marie-Gabrielle Duperron, Xueqiu Jian, Isabel C. Hostettler, Dianne H.K. van Dam-Nolen, Sander Lamballais, Mikolaj A. Pawlak, Cora E. Lewis, Amaia Carrion-Castillo, Theo G.M. van Erp, Céline S. Reinbold, Jean Shin, Markus Scholz, Asta K. Håberg, Anders Kämpe, Gloria H.Y. Li, Reut Avinun, Joshua R. Atkins, Fang-Chi Hsu, Alyssa R. Amod, Max Lam, Ami Tsuchida, Mariël W.A. Teunissen, Alexa S. Beiser, Frauke Beyer, Joshua C. Bis, Daniel Bos, R. Nick Bryan, Robin Bülow, Svenja Caspers, Gwenaëlle Catheline, Charlotte A.M. Cecil, Shareefa Dalvie, Jean-François Dartigues, Charles DeCarli, Maria Enlund-Cerullo, Judith M. Ford, Barbara Franke, Barry I. Freedman, Nele Friedrich, Melissa J. Green, Simon Haworth, Catherine Helmer, Per Hoffmann, Georg Homuth, M. Kamran Ikram, Clifford R. Jack, Neda Jahanshad, Christiane Jockwitz, Yoichiro Kamatani, Annchen R. Knodt, Shuo Li, Keane Lim, W. T. Longstreth, Fabio Macciardi, The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium, Outi Mäkitie, Bernard Mazoyer, Sarah E. Medland, Susumu Miyamoto, Susanne Moebus, Thomas H. Mosley, Ryan Muetzel, Thomas W. Mühleisen, Manabu Nagata, Soichiro Nakahara, Nicholette D. Palmer, Zdenka Pausova, Adrian Preda, Yann Quidé, William R. Reay, Gennady V. Roshchupkin, Reinhold Schmidt, Pamela J. Schreiner, Kazuya Setoh, Chin Yang Shapland, Stephen Sidney, Beate St Pourcain, Jason L. Stein, Yasuharu Tabara, Alexander Teumer, Anne Uhlmann, Aad van der Lugt, Meike W. Vernooij, David J. Werring, B. Gwen Windham, A. Veronica Witte, Katharina Wittfeld, Qiong Yang, Kazumichi Yoshida, Han G. Brunner, Quentin Le Grand, Kang Sim, Dan J. Stein, Donald W. Bowden, Murray J. Cairns, Ahmad R. Hariri, Ching-Lung Cheung, Sture Andersson, Arno Villringer, Tomas Paus, Sven Cichon, Vince D. Calhoun, Fabrice Crivello, Lenore J. Launer, Tonya White, Peter J. Koudstaal, Henry Houlden, Myriam Fornage, Fumihiko Matsuda, Hans J. Grabe, M. Arfan Ikram, Stéphanie Debette, Paul M. Thompson, Sudha Seshadri, Hieab H.H. Adams
doi: https://doi.org/10.1101/2020.07.15.191114
Maria J. Knol
1Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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  • ORCID record for Maria J. Knol
Raymond A. Poot
2Department of Cell Biology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Tavia E. Evans
3Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands
4Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Claudia L. Satizabal
5Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA
6The Framingham Heart Study, Framingham, MA, USA
7Department of Neurology, Boston University School of Medicine, Boston, MA, USA
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Aniket Mishra
8University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, Bordeaux, France
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Sandra van der Auwera
9Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
10German Centre of Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany
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Marie-Gabrielle Duperron
8University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, Bordeaux, France
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Xueqiu Jian
11Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
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Isabel C. Hostettler
12Stroke Research Centre, University College London, Institute of Neurology, London, UK
13Department of Neurosurgery, Klinikum rechts der Isar, University of Munich, Munich, Germany
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Dianne H.K. van Dam-Nolen
4Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Sander Lamballais
1Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Mikolaj A. Pawlak
3Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands
14Department of Neurology and Cerebrovascular Disorders, Poznań University of Medical Sciences, Poznań, Poland
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Cora E. Lewis
15Department of Epidemiology, School of Public Health, University of Alabama at Birmingham Shool of Medicine, Birmingham, AL, USA
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Amaia Carrion-Castillo
16Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands
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Theo G.M. van Erp
17Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, United States
18Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA
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Céline S. Reinbold
19Department of Biomedicine, University of Basel, Basel, Switzerland
20Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
21Department of Psychology, University of Oslo, Oslo, Norway
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Jean Shin
22The Hospital for Sick Children, University of Toronto, Toronto, Canada
23Department of Nutritional Sciences, University of Toronto, Toronto, Canada
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Markus Scholz
24Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
25LIFE Research Center for Civilization Disease, Leipzig, Germany
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Asta K. Håberg
26Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
27Department of Radiology and Nuclear Medicine, St. Olavs University Hospital, Trondheim, Norway
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Anders Kämpe
28Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
29Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
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Gloria H.Y. Li
30Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
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Reut Avinun
31Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA
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Joshua R. Atkins
32School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia
33Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW, Australia
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Fang-Chi Hsu
34Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA
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Alyssa R. Amod
35Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa
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Max Lam
36Research Division, Institute of Mental Health, Singapore
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Ami Tsuchida
37Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR5293, Université de Bordeaux, Bordeaux, France
38Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR5293, CNRS, Bordeaux, France
39Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR5293, CEA, Bordeaux, France
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Mariël W.A. Teunissen
40Department of Neurology, Maastricht University Medical Center+, Maastricht, The Netherlands
41Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
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Alexa S. Beiser
6The Framingham Heart Study, Framingham, MA, USA
7Department of Neurology, Boston University School of Medicine, Boston, MA, USA
42Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
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Frauke Beyer
43Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany
44Collaborative Research Center 1052 Obesity Mechanisms, Faculty of Medicine, University of Leipzig, Leipzig, Germany
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Joshua C. Bis
45Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA
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Daniel Bos
1Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
4Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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R. Nick Bryan
46The University of Texas at Austin Dell Medical School, Austin, TX, USA
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Robin Bülow
47Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany
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Svenja Caspers
48Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany
49JARA-BRAIN, Jülich-Aachen Research Alliance, Jülich, Germany
50Institute for Anatomy I, Medical Faculty, Heinrich Heine University Du□sseldorf, Du□sseldorf, Germany
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Gwenaëlle Catheline
51University of Bordeaux, CNRS, INCIA, UMR 5287, team NeuroImagerie et Cognition Humaine, Bordeaux, France
52EPHE-PSL University, Bordeaux, France
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Charlotte A.M. Cecil
1Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
53Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Shareefa Dalvie
35Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa
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Jean-François Dartigues
54University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team SEPIA, UMR 1219, Bordeaux, France
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Charles DeCarli
55Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA, USA
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Maria Enlund-Cerullo
56Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
57Folkhälsan Research Center, Helsinki, Finland
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Judith M. Ford
58San Francisco Veterans Administration Medical Center, San Francisco, CA, USA
59University of California San Francisco, San Francisco, CA, USA
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Barbara Franke
41Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
60Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands
61Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
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Barry I. Freedman
62Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA
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Nele Friedrich
63Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
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Melissa J. Green
64School of Psychiatry, the University of New South Wales, Sydney, NSW, Australia
65Neuroscience Research Australia, Sydney, NSW, Australia
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Simon Haworth
66MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
67Population Health Sciences, University of Bristol, Bristol, UK
68Bristol Dental School, University of Bristol, Bristol, UK
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Catherine Helmer
69University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team LEHA, UMR 1219, Bordeaux, France
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Per Hoffmann
19Department of Biomedicine, University of Basel, Basel, Switzerland
20Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
70Institute of Human Genetics, University of Bonn Medical School, Bonn, Germany
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Georg Homuth
71Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany
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M. Kamran Ikram
1Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
72Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Clifford R. Jack
73Department of Radiology, Mayo Clinic, Rochester, MN, USA
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Neda Jahanshad
74Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck USC School of Medicine, CA, USA
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Christiane Jockwitz
48Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany
75Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Yoichiro Kamatani
76Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Annchen R. Knodt
31Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA
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42Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
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Keane Lim
36Research Division, Institute of Mental Health, Singapore
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W. T. Longstreth
77Department of Neurology, University of Washington, Seattle, WA, USA
78Department of Epidemiology, University of Washington, Seattle, WA, USA
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Fabio Macciardi
79Laboratory of Molecular Psychiatry, Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, CA, USA
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Outi Mäkitie
28Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
29Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
56Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
57Folkhälsan Research Center, Helsinki, Finland
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Bernard Mazoyer
80Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique, Commissariat à l’Energie Atomique, et Université de Bordeaux, Bordeaux, France
81Centre Hospitalo-Universitaire de Bordeaux, Bordeaux, France
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Sarah E. Medland
82Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
83School of Psychology, University of Queensland, Brisbane, QLD, Australia
84Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
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Susumu Miyamoto
85Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Susanne Moebus
86Institute for Urban Public Health, University of Duisburg-Essen, Essen, Germany
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Thomas H. Mosley
87Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA
88Memory Impairment and Neurodegenerative Dementia (MIND) Center, Jackson, MS, USA
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Ryan Muetzel
1Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
53Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Thomas W. Mühleisen
19Department of Biomedicine, University of Basel, Basel, Switzerland
48Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany
89C. and O. Vogt Institute for Brain Research, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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Manabu Nagata
85Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Soichiro Nakahara
17Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, United States
90Unit 2, Candidate Discovery Science Labs, Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan
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Nicholette D. Palmer
91Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA
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Zdenka Pausova
22The Hospital for Sick Children, University of Toronto, Toronto, Canada
23Department of Nutritional Sciences, University of Toronto, Toronto, Canada
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Adrian Preda
92Department of Psychiatry, University of California Irvine, Irvine, CA, USA
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Yann Quidé
64School of Psychiatry, the University of New South Wales, Sydney, NSW, Australia
65Neuroscience Research Australia, Sydney, NSW, Australia
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William R. Reay
32School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia
33Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW, Australia
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Gennady V. Roshchupkin
1Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
4Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Reinhold Schmidt
93Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria
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Pamela J. Schreiner
94University of Minnesota School of Public Health, Minneapolis, MN, USA
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Kazuya Setoh
76Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Chin Yang Shapland
16Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands
66MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
67Population Health Sciences, University of Bristol, Bristol, UK
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Stephen Sidney
95Kaiser Permanente Division of Research, Oakland, CA, USA
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Beate St Pourcain
16Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands
61Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
66MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
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Jason L. Stein
96Department of Genetics & UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Yasuharu Tabara
76Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Alexander Teumer
97Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
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Anne Uhlmann
35Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa
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Aad van der Lugt
4Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Meike W. Vernooij
1Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
4Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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David J. Werring
12Stroke Research Centre, University College London, Institute of Neurology, London, UK
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B. Gwen Windham
87Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA
88Memory Impairment and Neurodegenerative Dementia (MIND) Center, Jackson, MS, USA
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A. Veronica Witte
43Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany
44Collaborative Research Center 1052 Obesity Mechanisms, Faculty of Medicine, University of Leipzig, Leipzig, Germany
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Katharina Wittfeld
9Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
10German Centre of Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany
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Qiong Yang
42Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
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Kazumichi Yoshida
85Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Han G. Brunner
98Department of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
99Department of Clinical Genetics MUMC+, GROW School of Oncology and developmental biology, and MHeNs School of Mental Health and Neuroscience, Maastricht University, The Netherlands
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Quentin Le Grand
100Bordeaux Population Health, University of Bordeaux INSERM U1219, Bordeaux, France
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Kang Sim
101West Region, Institute of Mental Health, Singapore
102Yong Loo Lin School of Medicine, National University of Singapore, Singapore
103Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
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Dan J. Stein
35Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa
104MRC Unit on Risk and Resilience, University of Cape Town, Cape Town, South Africa
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Donald W. Bowden
91Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA
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Murray J. Cairns
32School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia
33Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW, Australia
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Ahmad R. Hariri
31Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA
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Ching-Lung Cheung
30Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
105Centre for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
106Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
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Sture Andersson
56Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Arno Villringer
43Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany
107Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany
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Tomas Paus
108Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Canada
109Departments of Psychology and Psychiatry, University of Toronto, Toronto, Canada
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Sven Cichon
19Department of Biomedicine, University of Basel, Basel, Switzerland
20Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
48Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany
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Vince D. Calhoun
110Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Atlanta, GA, USA
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Fabrice Crivello
80Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique, Commissariat à l’Energie Atomique, et Université de Bordeaux, Bordeaux, France
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Lenore J. Launer
111Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute of Aging, The National Institutes of Health, Bethesda, MD, USA
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Tonya White
4Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
53Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Peter J. Koudstaal
72Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Henry Houlden
12Stroke Research Centre, University College London, Institute of Neurology, London, UK
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Myriam Fornage
11Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
112Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA
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Fumihiko Matsuda
76Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Hans J. Grabe
9Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
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M. Arfan Ikram
1Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Stéphanie Debette
100Bordeaux Population Health, University of Bordeaux INSERM U1219, Bordeaux, France
113Department of Neurology, Bordeaux University Hospital, Bordeaux, France
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Paul M. Thompson
74Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck USC School of Medicine, CA, USA
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Sudha Seshadri
5Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA
6The Framingham Heart Study, Framingham, MA, USA
7Department of Neurology, Boston University School of Medicine, Boston, MA, USA
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Hieab H.H. Adams
3Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands
4Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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  • For correspondence: h.adams@erasmusmc.nl
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Abstract

The size of the human head is determined by growth in the first years of life, while the rest of the body typically grows until early adulthood1. Such complex developmental processes are regulated by various genes and growth pathways2. Rare genetic syndromes have revealed genes that affect head size3, but the genetic drivers of variation in head size within the general population remain largely unknown. To elucidate biological pathways underlying the growth of the human head, we performed the largest genome-wide association study on human head size to date (N = 79,107). We identified 67 genetic loci, 50 of which are novel, and found that these loci are preferentially associated with head size and mostly independent from height. In subsequent neuroimaging analyses, the majority of genetic variants demonstrated widespread effects on the brain, whereas the effects of 17 variants could be localized to one or two specific brain regions. Through hypothesis-free approaches, we find a strong overlap of head size variants with both cancer pathways and cancer genes. Gene set analyses showed enrichment for different types of cancer and the p53, Wnt and ErbB signalling pathway. Genes overlapping or close to lead variants – such as TP53, PTEN and APC – were enriched for genes involved in macrocephaly syndromes (up to 37-fold) and high-fidelity cancer genes (up to 9-fold), whereas this enrichment was not seen for human height variants. This indicates that genes regulating early brain and cranial growth are associated with a propensity to neoplasia later in life, irrespective of height. Our results warrant further investigations of the link between head size and cancer, as well as its clinical implications in the general population.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵** These authors jointly supervised this work.

  • ↵† A full list of the consortium authors is provided below.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Genetic variants for head size share genes and pathways with cancer
Maria J. Knol, Raymond A. Poot, Tavia E. Evans, Claudia L. Satizabal, Aniket Mishra, Sandra van der Auwera, Marie-Gabrielle Duperron, Xueqiu Jian, Isabel C. Hostettler, Dianne H.K. van Dam-Nolen, Sander Lamballais, Mikolaj A. Pawlak, Cora E. Lewis, Amaia Carrion-Castillo, Theo G.M. van Erp, Céline S. Reinbold, Jean Shin, Markus Scholz, Asta K. Håberg, Anders Kämpe, Gloria H.Y. Li, Reut Avinun, Joshua R. Atkins, Fang-Chi Hsu, Alyssa R. Amod, Max Lam, Ami Tsuchida, Mariël W.A. Teunissen, Alexa S. Beiser, Frauke Beyer, Joshua C. Bis, Daniel Bos, R. Nick Bryan, Robin Bülow, Svenja Caspers, Gwenaëlle Catheline, Charlotte A.M. Cecil, Shareefa Dalvie, Jean-François Dartigues, Charles DeCarli, Maria Enlund-Cerullo, Judith M. Ford, Barbara Franke, Barry I. Freedman, Nele Friedrich, Melissa J. Green, Simon Haworth, Catherine Helmer, Per Hoffmann, Georg Homuth, M. Kamran Ikram, Clifford R. Jack, Neda Jahanshad, Christiane Jockwitz, Yoichiro Kamatani, Annchen R. Knodt, Shuo Li, Keane Lim, W. T. Longstreth, Fabio Macciardi, The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium, Outi Mäkitie, Bernard Mazoyer, Sarah E. Medland, Susumu Miyamoto, Susanne Moebus, Thomas H. Mosley, Ryan Muetzel, Thomas W. Mühleisen, Manabu Nagata, Soichiro Nakahara, Nicholette D. Palmer, Zdenka Pausova, Adrian Preda, Yann Quidé, William R. Reay, Gennady V. Roshchupkin, Reinhold Schmidt, Pamela J. Schreiner, Kazuya Setoh, Chin Yang Shapland, Stephen Sidney, Beate St Pourcain, Jason L. Stein, Yasuharu Tabara, Alexander Teumer, Anne Uhlmann, Aad van der Lugt, Meike W. Vernooij, David J. Werring, B. Gwen Windham, A. Veronica Witte, Katharina Wittfeld, Qiong Yang, Kazumichi Yoshida, Han G. Brunner, Quentin Le Grand, Kang Sim, Dan J. Stein, Donald W. Bowden, Murray J. Cairns, Ahmad R. Hariri, Ching-Lung Cheung, Sture Andersson, Arno Villringer, Tomas Paus, Sven Cichon, Vince D. Calhoun, Fabrice Crivello, Lenore J. Launer, Tonya White, Peter J. Koudstaal, Henry Houlden, Myriam Fornage, Fumihiko Matsuda, Hans J. Grabe, M. Arfan Ikram, Stéphanie Debette, Paul M. Thompson, Sudha Seshadri, Hieab H.H. Adams
bioRxiv 2020.07.15.191114; doi: https://doi.org/10.1101/2020.07.15.191114
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Genetic variants for head size share genes and pathways with cancer
Maria J. Knol, Raymond A. Poot, Tavia E. Evans, Claudia L. Satizabal, Aniket Mishra, Sandra van der Auwera, Marie-Gabrielle Duperron, Xueqiu Jian, Isabel C. Hostettler, Dianne H.K. van Dam-Nolen, Sander Lamballais, Mikolaj A. Pawlak, Cora E. Lewis, Amaia Carrion-Castillo, Theo G.M. van Erp, Céline S. Reinbold, Jean Shin, Markus Scholz, Asta K. Håberg, Anders Kämpe, Gloria H.Y. Li, Reut Avinun, Joshua R. Atkins, Fang-Chi Hsu, Alyssa R. Amod, Max Lam, Ami Tsuchida, Mariël W.A. Teunissen, Alexa S. Beiser, Frauke Beyer, Joshua C. Bis, Daniel Bos, R. Nick Bryan, Robin Bülow, Svenja Caspers, Gwenaëlle Catheline, Charlotte A.M. Cecil, Shareefa Dalvie, Jean-François Dartigues, Charles DeCarli, Maria Enlund-Cerullo, Judith M. Ford, Barbara Franke, Barry I. Freedman, Nele Friedrich, Melissa J. Green, Simon Haworth, Catherine Helmer, Per Hoffmann, Georg Homuth, M. Kamran Ikram, Clifford R. Jack, Neda Jahanshad, Christiane Jockwitz, Yoichiro Kamatani, Annchen R. Knodt, Shuo Li, Keane Lim, W. T. Longstreth, Fabio Macciardi, The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium, Outi Mäkitie, Bernard Mazoyer, Sarah E. Medland, Susumu Miyamoto, Susanne Moebus, Thomas H. Mosley, Ryan Muetzel, Thomas W. Mühleisen, Manabu Nagata, Soichiro Nakahara, Nicholette D. Palmer, Zdenka Pausova, Adrian Preda, Yann Quidé, William R. Reay, Gennady V. Roshchupkin, Reinhold Schmidt, Pamela J. Schreiner, Kazuya Setoh, Chin Yang Shapland, Stephen Sidney, Beate St Pourcain, Jason L. Stein, Yasuharu Tabara, Alexander Teumer, Anne Uhlmann, Aad van der Lugt, Meike W. Vernooij, David J. Werring, B. Gwen Windham, A. Veronica Witte, Katharina Wittfeld, Qiong Yang, Kazumichi Yoshida, Han G. Brunner, Quentin Le Grand, Kang Sim, Dan J. Stein, Donald W. Bowden, Murray J. Cairns, Ahmad R. Hariri, Ching-Lung Cheung, Sture Andersson, Arno Villringer, Tomas Paus, Sven Cichon, Vince D. Calhoun, Fabrice Crivello, Lenore J. Launer, Tonya White, Peter J. Koudstaal, Henry Houlden, Myriam Fornage, Fumihiko Matsuda, Hans J. Grabe, M. Arfan Ikram, Stéphanie Debette, Paul M. Thompson, Sudha Seshadri, Hieab H.H. Adams
bioRxiv 2020.07.15.191114; doi: https://doi.org/10.1101/2020.07.15.191114

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