학술논문

Genetic variants for head size share genes and pathways with cancer.
Document Type
Academic Journal
Author
Knol MJ; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Poot RA; Department of Cell Biology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Evans TE; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Satizabal CL; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA; The Framingham Heart Study, Framingham, MA, USA; Department of Neurology, Boston University School of Medicine, Boston, MA, USA.; Mishra A; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, Bordeaux, France.; Sargurupremraj M; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA.; van der Auwera S; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; German Centre of Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany.; Duperron MG; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, Bordeaux, France.; Jian X; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.; Hostettler IC; Stroke Research Centre, University College London, Institute of Neurology, London, UK; Department of Neurosurgery, Klinikum rechts der Isar, University of Munich, Munich, Germany; Neurosurgical Department, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.; van Dam-Nolen DHK; Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Lamballais S; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Pawlak MA; Department of Neurology, Poznań University of Medical Sciences, Poznań, Poland; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.; Lewis CE; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA.; Carrion-Castillo A; Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.; van Erp TGM; Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA; Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA, USA.; Reinbold CS; Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland; Institute of Computational Life Sciences, Zurich University of Applied Sciences, Wädenswil, Switzerland.; Shin J; The Hospital for Sick Children, University of Toronto, Toronto, Canada; Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada.; Scholz M; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; LIFE Research Center for Civilization Disease, Leipzig, Germany.; Håberg AK; Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Radiology and Nuclear Medicine, St. Olavs University Hospital, Trondheim, Norway.; Kämpe A; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.; Li GHY; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.; Avinun R; Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA.; Atkins JR; School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia; Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW, Australia.; Hsu FC; Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, USA.; Amod AR; Department of Child and Adolescent Psychiatry, TU Dresden, Dresden, Germany.; Lam M; North Region, Institute of Mental Health, Singapore, Singapore; Population and Global Health, LKC Medicine, Nanyang Technological University, Singapore, Singapore.; Tsuchida A; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, Bordeaux, France; Groupe d'imagerie neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR 5293, CNRS, CEA, Université de Bordeaux, Bordeaux, France.; Teunissen MWA; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands.; Aygün N; Department of Genetics UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Patel Y; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.; Liang D; Department of Genetics UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Beiser AS; The Framingham Heart Study, Framingham, MA, USA; Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.; Beyer F; Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany; Collaborative Research Center 1052 Obesity Mechanisms, Faculty of Medicine, University of Leipzig, Leipzig, Germany; Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany.; Bis JC; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.; Bos D; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Bryan RN; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.; Bülow R; Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.; Caspers S; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.; Catheline G; University of Bordeaux, CNRS, INCIA, UMR 5287, team NeuroImagerie et Cognition Humaine, Bordeaux, France; EPHE-PSL University, Bordeaux, France.; Cecil CAM; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Dalvie S; Department of Child and Adolescent Psychiatry, TU Dresden, Dresden, Germany.; Dartigues JF; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team SEPIA, UMR 1219, Bordeaux, France.; DeCarli C; Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA, USA.; Enlund-Cerullo M; Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland.; Ford JM; San Francisco Veterans Administration Medical Center, San Francisco, CA, USA; University of California, San Francisco, San Francisco, CA, USA.; Franke B; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Radboud University, Nijmegen, the Netherlands.; Freedman BI; Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Friedrich N; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.; Green MJ; School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia.; Haworth S; Bristol Dental School, University of Bristol, Bristol, UK.; Helmer C; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team LEHA, UMR 1219, Bordeaux, France.; Hoffmann P; Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland; Institute of Human Genetics, University of Bonn Medical School, Bonn, Germany.; Homuth G; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.; Ikram MK; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Jack CR Jr; Department of Radiology, Mayo Clinic, Rochester, MN, USA.; Jahanshad N; Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck USC School of Medicine, Los Angeles, CA, USA.; Jockwitz C; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Medical Faculty, Aachen, Germany.; Kamatani Y; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.; Knodt AR; Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA.; Li S; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.; Lim K; Research Division, Institute of Mental Health, Singapore, Singapore.; Longstreth WT; Department of Neurology, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.; Macciardi F; Laboratory of Molecular Psychiatry, Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, Irvine, CA, USA.; Mäkitie O; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden; Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland.; Mazoyer B; Groupe d'imagerie neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR 5293, CNRS, CEA, Université de Bordeaux, Bordeaux, France; Centre Hospitalo-Universitaire de Bordeaux, Bordeaux, France.; Medland SE; Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Psychology, University of Queensland, Brisbane, QLD, Australia; Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; Miyamoto S; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.; Moebus S; Institute for Urban Public Health, University of Duisburg-Essen, Essen, Germany.; Mosley TH; Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA; Memory Impairment and Neurodegenerative Dementia (MIND) Center, Jackson, MS, USA.; Muetzel R; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Mühleisen TW; Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; C. and O. Vogt Institute for Brain Research, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.; Nagata M; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.; Nakahara S; Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA; Unit 2, Candidate Discovery Science Labs, Drug Discovery Research, Astellas Pharma Inc, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.; Palmer ND; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Pausova Z; The Hospital for Sick Children, University of Toronto, Toronto, Canada; Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada.; Preda A; Department of Psychiatry, University of California, Irvine, Irvine, CA, USA.; Quidé Y; School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia.; Reay WR; School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia; Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW, Australia.; Roshchupkin GV; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Schmidt R; Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.; Schreiner PJ; University of Minnesota School of Public Health, Minneapolis, MN, USA.; Setoh K; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.; Shapland CY; Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Population Health Sciences, University of Bristol, Bristol, UK.; Sidney S; Kaiser Permanente Division of Research, Oakland, CA, USA.; St Pourcain B; Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Radboud University, Nijmegen, the Netherlands; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Stein JL; Department of Genetics UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Tabara Y; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.; Teumer A; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.; Uhlmann A; Department of Child and Adolescent Psychiatry, TU Dresden, Dresden, Germany.; van der Lugt A; Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Vernooij MW; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Werring DJ; Stroke Research Centre, University College London, Institute of Neurology, London, UK.; Windham BG; Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA; Memory Impairment and Neurodegenerative Dementia (MIND) Center, Jackson, MS, USA.; Witte AV; Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany; Collaborative Research Center 1052 Obesity Mechanisms, Faculty of Medicine, University of Leipzig, Leipzig, Germany; Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany.; Wittfeld K; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; German Centre of Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany.; Yang Q; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.; Yoshida K; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.; Brunner HG; Department of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Clinical Genetics MUMC+, GROW School of Oncology and Developmental Biology, and MHeNs School of Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.; Le Grand Q; Bordeaux Population Health, University of Bordeaux, INSERM U1219, Bordeaux, France.; Sim K; West Region, Institute of Mental Health, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.; Stein DJ; Department of Child and Adolescent Psychiatry, TU Dresden, Dresden, Germany; SAMRC Unit on Risk and Resilience, University of Cape Town, Cape Town, South Africa.; Bowden DW; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Cairns MJ; School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia; Centre for Brain and Mental Health Research, Hunter Medical Research Institute, Newcastle, NSW, Australia.; Hariri AR; Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA.; Cheung CL; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Centre for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.; Andersson S; Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Villringer A; Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany; Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany.; Paus T; Departments of Psychiatry and Neuroscience, Faculty of Medicine and Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, QC, Canada; Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, QC, Canada.; Cichon S; Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.; Calhoun VD; Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS) {Georgia State, Georgia Tech, Emory}, Atlanta, GA, USA.; Crivello F; Groupe d'imagerie neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR 5293, CNRS, CEA, Université de Bordeaux, Bordeaux, France.; Launer LJ; Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute of Aging, The National Institutes of Health, Bethesda, MD, USA.; White T; Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Koudstaal PJ; Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Houlden H; Stroke Research Centre, University College London, Institute of Neurology, London, UK.; Fornage M; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.; Matsuda F; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.; Grabe HJ; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.; Ikram MA; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Debette S; Bordeaux Population Health, University of Bordeaux, INSERM U1219, Bordeaux, France; Department of Neurology, Bordeaux University Hospital, Bordeaux, France.; Thompson PM; Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck USC School of Medicine, Los Angeles, CA, USA.; Seshadri S; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA; The Framingham Heart Study, Framingham, MA, USA; Department of Neurology, Boston University School of Medicine, Boston, MA, USA.; Adams HHH; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands; Latin American Brain Health (BrainLat), Universidad Adolfo Ibáñez, Santiago, Chile. Electronic address: hieab.adams@radboudumc.nl.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE
Subject
Language
English
Abstract
The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.
Competing Interests: Declaration of interests H.H. and I.C.H. received funding from Alzheimer’s Research UK and the Dunhill Medical Trust Foundation. M.A.P. reported receiving grants and personal and travel fees from Roche, Novartis, Merck, and Biogen outside the submitted work. M. Scholz receives funding from Pfizer Inc. for a project not related to this research. C.D. serves as a consultant of Novartis Pharmaceuticals. B.F. has received educational speaking fees from Medice. N.J. and P.M.T. are MPIs of a research grant from Biogen Inc. for work unrelated to the contents of this manuscript. D.J.W. received funding from the Stroke Foundation/British Heart Foundation. D.J.S. has received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen. H.H. received funding from MRC, Wellcome Trust, and NIHR UCLH BRC. H.J.G. has received travel grants and speaker’s honoraria from Fresenius Medical Care, Neuraxpharm, and Janssen Cilag as well as research funding from Fresenius Medical Care.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)