Genetic variants for head size share genes and pathways with cancer.
Journal: Cell reports. Medicine
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Affiliated Institutions: Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. Department of Cell Biology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. 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. 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. University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR , Bordeaux, France. Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; German Centre of Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany. Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA. 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. Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands. Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands. Department of Neurology, Poznań University of Medical Sciences, Poznań, Poland; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands. Department of Epidemiology, School of Public Health, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA. Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands. 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. 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. The Hospital for Sick Children, University of Toronto, Toronto, Canada; Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; LIFE Research Center for Civilization Disease, Leipzig, Germany. 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. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA. 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. Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, USA. Department of Child and Adolescent Psychiatry, TU Dresden, Dresden, Germany. North Region, Institute of Mental Health, Singapore, Singapore; Population and Global Health, LKC Medicine, Nanyang Technological University, Singapore, Singapore. University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR , Bordeaux, France; Groupe d'imagerie neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR , CNRS, CEA, Université de Bordeaux, Bordeaux, France. Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands. Department of Genetics UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada. 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. Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany; Collaborative Research Center Obesity Mechanisms, Faculty of Medicine, University of Leipzig, Leipzig, Germany; Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA. 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. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA. Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany. Institute of Neuroscience and Medicine (INM-), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. University of Bordeaux, CNRS, INCIA, UMR , team NeuroImagerie et Cognition Humaine, Bordeaux, France; EPHE-PSL University, Bordeaux, France. 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. University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team SEPIA, UMR , Bordeaux, France. Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA, USA. Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland. San Francisco Veterans Administration Medical Center, San Francisco, CA, USA; University of California, San Francisco, San Francisco, CA, USA. 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. Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia. Bristol Dental School, University of Bristol, Bristol, UK. University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team LEHA, UMR , Bordeaux, France. 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. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. Department of Radiology, Mayo Clinic, Rochester, MN, USA. Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck USC School of Medicine, Los Angeles, CA, USA. Institute of Neuroscience and Medicine (INM-), Research Centre Jülich, Jülich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Medical Faculty, Aachen, Germany. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. Research Division, Institute of Mental Health, Singapore, Singapore. Department of Neurology, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA. Laboratory of Molecular Psychiatry, Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, Irvine, CA, USA. 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. Groupe d'imagerie neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR , CNRS, CEA, Université de Bordeaux, Bordeaux, France; Centre Hospitalo-Universitaire de Bordeaux, Bordeaux, France. 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. Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Institute for Urban Public Health, University of Duisburg-Essen, Essen, Germany. Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA; Memory Impairment and Neurodegenerative Dementia (MIND) Center, Jackson, MS, USA. Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Neuroscience and Medicine (INM-), Research Centre Jülich, Jülich, Germany; C. and O. Vogt Institute for Brain Research, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA; Unit , Candidate Discovery Science Labs, Drug Discovery Research, Astellas Pharma Inc, Miyukigaoka, Tsukuba, Ibaraki -, Japan. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA. Department of Psychiatry, University of California, Irvine, Irvine, CA, USA. Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria. University of Minnesota School of Public Health, Minneapolis, MN, USA. 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. Kaiser Permanente Division of Research, Oakland, CA, USA. 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. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. Stroke Research Centre, University College London, Institute of Neurology, London, UK. 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. Bordeaux Population Health, University of Bordeaux, INSERM U, Bordeaux, France. 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. Department of Child and Adolescent Psychiatry, TU Dresden, Dresden, Germany; SAMRC Unit on Risk and Resilience, University of Cape Town, Cape Town, South Africa. 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. Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany; Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany. 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. 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-), Research Centre Jülich, Jülich, Germany. Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS) {Georgia State, Georgia Tech, Emory}, Atlanta, GA, USA. Groupe d'imagerie neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR , CNRS, CEA, Université de Bordeaux, Bordeaux, France. Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute of Aging, The National Institutes of Health, Bethesda, MD, USA. 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. Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. 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. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. Bordeaux Population Health, University of Bordeaux, INSERM U, Bordeaux, France; Department of Neurology, Bordeaux University Hospital, Bordeaux, France. 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.
Abstract summary
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.Authors & Co-authors: Knol Maria J MJ Poot Raymond A RA Evans Tavia E TE Satizabal Claudia L CL Mishra Aniket A Sargurupremraj Muralidharan M van der Auwera Sandra S Duperron Marie-Gabrielle MG Jian Xueqiu X Hostettler Isabel C IC van Dam-Nolen Dianne H K DHK Lamballais Sander S Pawlak Mikolaj A MA Lewis Cora E CE Carrion-Castillo Amaia A van Erp Theo G M TGM Reinbold Céline S CS Shin Jean J Scholz Markus M Håberg Asta K AK Kämpe Anders A Li Gloria H Y GHY Avinun Reut R Atkins Joshua R JR Hsu Fang-Chi FC Amod Alyssa R AR Lam Max M Tsuchida Ami A Teunissen Mariël W A MWA Aygün Nil N Patel Yash Y Liang Dan D Beiser Alexa S AS Beyer Frauke F Bis Joshua C JC Bos Daniel D Bryan R Nick RN Bülow Robin R Caspers Svenja S Catheline Gwenaëlle G Cecil Charlotte A M CAM Dalvie Shareefa S Dartigues Jean-François JF DeCarli Charles C Enlund-Cerullo Maria M Ford Judith M JM Franke Barbara B Freedman Barry I BI Friedrich Nele N Green Melissa J MJ Haworth Simon S Helmer Catherine C Hoffmann Per P Homuth Georg G Ikram M Kamran MK Jack Clifford R CR Jahanshad Neda N Jockwitz Christiane C Kamatani Yoichiro Y Knodt Annchen R AR Li Shuo S Lim Keane K Longstreth W T WT Macciardi Fabio F Mäkitie Outi O Mazoyer Bernard B Medland Sarah E SE Miyamoto Susumu S Moebus Susanne S Mosley Thomas H TH Muetzel Ryan R Mühleisen Thomas W TW Nagata Manabu M Nakahara Soichiro S Palmer Nicholette D ND Pausova Zdenka Z Preda Adrian A Quidé Yann Y Reay William R WR Roshchupkin Gennady V GV Schmidt Reinhold R Schreiner Pamela J PJ Setoh Kazuya K Shapland Chin Yang CY Sidney Stephen S St Pourcain Beate B Stein Jason L JL Tabara Yasuharu Y Teumer Alexander A Uhlmann Anne A van der Lugt Aad A Vernooij Meike W MW Werring David J DJ Windham B Gwen BG Witte A Veronica AV Wittfeld Katharina K Yang Qiong Q Yoshida Kazumichi K Brunner Han G HG Le Grand Quentin Q Sim Kang K Stein Dan J DJ Bowden Donald W DW Cairns Murray J MJ Hariri Ahmad R AR Cheung Ching-Lung CL Andersson Sture S Villringer Arno A Paus Tomas T Cichon Sven S Calhoun Vince D VD Crivello Fabrice F Launer Lenore J LJ White Tonya T Koudstaal Peter J PJ Houlden Henry H Fornage Myriam M Matsuda Fumihiko F Grabe Hans J HJ Ikram M Arfan MA Debette Stéphanie S Thompson Paul M PM Seshadri Sudha S Adams Hieab H H HHH
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Citations :Authors : 126
Identifiers
Doi : 10.1016/j.xcrm.2024.101529SSN : 2666-3791