Genetic variants associated with longitudinal changes in brain structure across the lifespan.
Journal: Nature neuroscience
Volume: 25
Issue: 4
Year of Publication: 2022
Affiliated Institutions: Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands. r.m.brouwer@vu.nl. Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands. Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA. Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Psychiatry and Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA. American Psychiatric Association, Washington, DC, USA. Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles, CA, USA. Biogen Research and Development, Cambridge, MA, USA. Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands. Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, School of Medicine, Universidad Complutense, Madrid, Spain. NORMENT Centre, University of Oslo, Oslo, Norway. INSERM U Trajectoires Développementales en Psychiatrie, Ecole Normale Supérieure Paris-Saclay, Université Paris Saclay, Université Paris Cité, CNRS UMR ; Centre Borelli, Gif-sur-Yvette, France. Valdecilla Biomedical Research Institute (IDIVAL), Marqués de Valdecilla University Hospital (HUMV), School of Medicine, University of Cantabria, Santander, Spain. Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. Lothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK. Department of Child and Adolescent Psychiatry/Psychology, Sophia Children's Hospital, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands. Psychosomatic and CL Psychiatry, Oslo University Hospital, Oslo, Norway. Brain Dynamics Centre, Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia. Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany. Centre for Neuroimaging, Cognition and Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Department of Neurology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. Institute for Translational Psychiatry, University of Münster, Münster, Germany. Section of Systems Neuroscience, Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany. Université Paris-Saclay, CEA, Neurospin, Gif-sur-Yvette, France. University of Groningen, University Medical Center Groningen, Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Groningen, The Netherlands. Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa. Clinic for Radiology, University Hospital Münster, Münster, Germany. Departments of Experimental and Clinical Psychology, Amsterdam, The Netherlands. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. Physikalisch-Technische Bundesanstalt, Berlin, Germany. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, The Netherlands. Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Science and Technology for Brain-Inspired Intelligence and MoE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China. Centre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, NSW, Australia. Institute of Neuroscience and Medicine (INM-), Research Centre Jülich, Jülich, Germany. Department of Psychiatry and Psychotherapy, University Hospital LMU, Munich, Germany. School of Psychiatry, University of New South Wales, Sydney, NSW, Australia. Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany. Department of Psychiatry, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. School of Psychology and Centre for Brain Research, University of Auckland, Auckland, New Zealand. Neuroscience Research Australia, Sydney, NSW, Australia. Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands. Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany. Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, MD, USA. Department of Radiology, IDIVAL, Marqués de Valdecilla University Hospital, Santander, Spain. Department of Radiology & Nuclear Medicine, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands. Department of Neurology, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands. German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany. Laboratory of Integrative Neuroscience (LiNC), Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Mathematics and Statistics, Curtin University, Perth, WA, Australia. Centre for Neuroimaging, Cognition and Genomics (NICOG), School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. NORMENT Centre of Excellence, Department of Clinical Science, University of Bergen, Bergen, Norway. Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany. CIBERSAM, Biomedical Research Network on Mental Health Area, Santander, Spain. Department of Genetic Epidemiology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Department of Genetics & UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. Academic Unit for Psychiatry of Old Age, University of Melbourne, Parkville, VIC, Australia. Department of Psychiatry, University of Melbourne, Melbourne VIC, Australia. Discipline of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. NORMENT Centre, Oslo University Hospital, Oslo, Norway. Department of Psychology, University of Oslo, Oslo, Norway. Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands. Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Department of Psychiatry, University of Vermont, Burlington, VT, USA. Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK. Charité Universitätsmedizin Berlin, Berlin, Germany. University of Groningen, University Medical Center Groningen, Department of Child and Adolescent Psychiatry & Accare Child Study Center, Groningen, The Netherlands. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, CNRS UMR , Université de Bordeaux, Centre Broca Nouvelle-Aquitaine, Bordeaux, France. Unit for Psychosomatic Medicine and C-L Psychiatry, University of Oslo, Oslo, Norway. Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Emma Neuroscience Group, Department of Pediatrics, Amsterdam Reproduction & Development, Amsterdam, The Netherlands. Department of Child and Adolescent Psychiatry, University Medical Center Goettingen, Göttingen, Germany. National Institute of Developmental Psychiatry for Children and Adolescents (INPD), CNPq, São Paulo, Brazil. Center for Population Neuroscience and Precision Medicine (PONS), Institute for Science and Technology for Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, China. West Region, Institute of Mental Health, Singapore, Singapore. Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany. SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute for Health, Berlin, Germany. Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands. h.e.hulshoffpol@uu.nl.
Abstract summary
Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.Authors & Co-authors: Brouwer Rachel M RM Klein Marieke M Grasby Katrina L KL Schnack Hugo G HG Jahanshad Neda N Teeuw Jalmar J Thomopoulos Sophia I SI Sprooten Emma E Franz Carol E CE Gogtay Nitin N Kremen William S WS Panizzon Matthew S MS Olde Loohuis Loes M LM Whelan Christopher D CD Aghajani Moji M Alloza Clara C Alnæs Dag D Artiges Eric E Ayesa-Arriola Rosa R Barker Gareth J GJ Bastin Mark E ME Blok Elisabet E Bøen Erlend E Breukelaar Isabella A IA Bright Joanna K JK Buimer Elizabeth E L EEL Bülow Robin R Cannon Dara M DM Ciufolini Simone S Crossley Nicolas A NA Damatac Christienne G CG Dazzan Paola P de Mol Casper L CL de Zwarte Sonja M C SMC Desrivières Sylvane S Díaz-Caneja Covadonga M CM Doan Nhat Trung NT Dohm Katharina K Fröhner Juliane H JH Goltermann Janik J Grigis Antoine A Grotegerd Dominik D Han Laura K M LKM Harris Mathew A MA Hartman Catharina A CA Heany Sarah J SJ Heindel Walter W Heslenfeld Dirk J DJ Hohmann Sarah S Ittermann Bernd B Jansen Philip R PR Janssen Joost J Jia Tianye T Jiang Jiyang J Jockwitz Christiane C Karali Temmuz T Keeser Daniel D Koevoets Martijn G J C MGJC Lenroot Rhoshel K RK Malchow Berend B Mandl René C W RCW Medel Vicente V Meinert Susanne S Morgan Catherine A CA Mühleisen Thomas W TW Nabulsi Leila L Opel Nils N de la Foz Víctor Ortiz-García VO Overs Bronwyn J BJ Paillère Martinot Marie-Laure ML Redlich Ronny R Marques Tiago Reis TR Repple Jonathan J Roberts Gloria G Roshchupkin Gennady V GV Setiaman Nikita N Shumskaya Elena E Stein Frederike F Sudre Gustavo G Takahashi Shun S Thalamuthu Anbupalam A Tordesillas-Gutiérrez Diana D van der Lugt Aad A van Haren Neeltje E M NEM Wardlaw Joanna M JM Wen Wei W Westeneng Henk-Jan HJ Wittfeld Katharina K Zhu Alyssa H AH Zugman Andre A Armstrong Nicola J NJ Bonfiglio Gaia G Bralten Janita J Dalvie Shareefa S Davies Gail G Di Forti Marta M Ding Linda L Donohoe Gary G Forstner Andreas J AJ Gonzalez-Peñas Javier J Guimaraes Joao P O F T JPOFT Homuth Georg G Hottenga Jouke-Jan JJ Knol Maria J MJ Kwok John B J JBJ Le Hellard Stephanie S Mather Karen A KA Milaneschi Yuri Y Morris Derek W DW Nöthen Markus M MM Papiol Sergi S Rietschel Marcella M Santoro Marcos L ML Steen Vidar M VM Stein Jason L JL Streit Fabian F Tankard Rick M RM Teumer Alexander A van 't Ent Dennis D van der Meer Dennis D van Eijk Kristel R KR Vassos Evangelos E Vázquez-Bourgon Javier J Witt Stephanie H SH Adams Hieab H H HHH Agartz Ingrid I Ames David D Amunts Katrin K Andreassen Ole A OA Arango Celso C Banaschewski Tobias T Baune Bernhard T BT Belangero Sintia I SI Bokde Arun L W ALW Boomsma Dorret I DI Bressan Rodrigo A RA Brodaty Henry H Buitelaar Jan K JK Cahn Wiepke W Caspers Svenja S Cichon Sven S Crespo-Facorro Benedicto B Cox Simon R SR Dannlowski Udo U Elvsåshagen Torbjørn T Espeseth Thomas T Falkai Peter G PG Fisher Simon E SE Flor Herta H Fullerton Janice M JM Garavan Hugh H Gowland Penny A PA Grabe Hans J HJ Hahn Tim T Heinz Andreas A Hillegers Manon M Hoare Jacqueline J Hoekstra Pieter J PJ Ikram Mohammad A MA Jackowski Andrea P AP Jansen Andreas A Jönsson Erik G EG Kahn Rene S RS Kircher Tilo T Korgaonkar Mayuresh S MS Krug Axel A Lemaitre Herve H Malt Ulrik F UF Martinot Jean-Luc JL McDonald Colm C Mitchell Philip B PB Muetzel Ryan L RL Murray Robin M RM Nees Frauke F Nenadić Igor I Oosterlaan Jaap J Ophoff Roel A RA Pan Pedro M PM Penninx Brenda W J H BWJH Poustka Luise L Sachdev Perminder S PS Salum Giovanni A GA Schofield Peter R PR Schumann Gunter G Shaw Philip P Sim Kang K Smolka Michael N MN Stein Dan J DJ Trollor Julian N JN van den Berg Leonard H LH Veldink Jan H JH Walter Henrik H Westlye Lars T LT Whelan Robert R White Tonya T Wright Margaret J MJ Medland Sarah E SE Franke Barbara B Thompson Paul M PM Hulshoff Pol Hilleke E HE
Study Outcome
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Citations : Hedman AM, van Haren NE, Schnack HG, Kahn RS & Hulshoff Pol HE Human brain changes across the life span: a review of 56 longitudinal magnetic resonance imaging studies. Hum Brain Mapp 33, 1987–2002 (2012).;Fischl B. et al. Whole Brain Segmentation: Automated Labeling of Neuroanatomical Structures in the Human Brain. Neuron 33, 341–355 (2002).Authors : 201
Identifiers
Doi : 10.1038/s41593-022-01042-4SSN : 1546-1726