Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.
Journal: Nature genetics
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Affiliated Institutions: Brain and Mental Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA. Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. Department of Neurology, Alpert Medical School of Brown University, Providence, RI, USA. Academic Unit Psychiatry of Old Age, University of Melbourne, Melbourne, Victoria, Australia. Universite Lille, U-RID-AGE-LabEx DISTALZ-Risk Factors and Molecular Determinants of Aging Diseases, Lille, France. Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. Departments of Psychiatry and Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Mathematics and Statistics, Curtin University, Perth, Western Australia, Australia. Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Centre for Clinical Brain Sciences and Edinburgh Imaging, University of Edinburgh, Edinburgh, UK. Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA. Brain Center University Medical Center Utrecht, Utrecht, The Netherlands. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, The Netherlands. Centre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia. Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg University, Regensburg, Germany. Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands. Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS)-Georgia State, Georgia Tech and Emory University, Atlanta, GA, USA. Pennington Biomedical Research Center, Baton Rouge, LA, USA. Cerebral Imaging Centre, Douglas Research Centre, Montreal, Quebec, Canada. Lieber Institute for Brain Development, Baltimore, MD, USA. Laboratory of Neuro Imaging, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA. Institute of Neuroscience and Medicine (INM-), Research Center Jülich, Jülich, Germany. HU Virgen del Rocio, Instituto de Investigacion Biomedica IBIS-CSIC, Universidad de Sevilla, CIBERSAM, Sevilla, Spain. CNRS, IMN, UMR , University of Bordeaux, Bordeaux, France. Center for Multimodal Imaging and Genetics, La Jolla, CA, USA. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York City, NY, USA. School of Psychology and Counselling, Queensland University of Technology, Brisbane, Queensland, Australia. INSERM U, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France. Imaging of Dementia and Aging Laboratory, Department of Neurology, University of California, Davis, Sacramento, CA, USA. Department of Neurology, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium. Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. Translational Developmental Neuroscience Section, Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Dresden, Germany. German Center of Mental Health (DZPG), Partner Site Berlin/Potsdam, Berlin, Germany. Department of Psychology, University of Oslo, Oslo, Norway. Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. INSERM U, Paris Saclay University, Gif-sur-Yvette, France. Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands. Department of Neurology, University of California, Davis, Davis, CA, USA. Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA. Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. Department of Medicine (Genetics), Mass General Brigham and Harvard Medical School, Boston, MA, USA. Central Institute of Mental Health, Mannheim, Germany. Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany. Icelandic Heart Association, Kopavogur, Iceland. Department of Neuromedicine and Movement, NTNU Science, Trondheim, Norway. Norwegian Centre for Mental Health Research (NORMENT), Department of Mental Health and Addiction, University of Oslo, Oslo, Norway. Product Development, Genentech, Inc., South San Francisco, CA, USA. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore City, Singapore. Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. Max Planck Institute of Psychiatry, Munich, Germany. Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria. German Centre for Neurodegenerative Diseases (DZNE)-Site Rostock/Greifswald, Greifswald, Germany. Department of Psychiatry, Brain Health Institute, Rutgers University, Piscataway, NJ, USA. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. Department of Radiology, University Clinic Greifswald, Greifswald, Germany. Departments of Epidemiology and Neurology, Erasmus MC, Rotterdam, The Netherlands. Department of Psychiatry and Mental Health, Neuroscience Institute, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa. Department of Radiology, Mayo Clinic, Rochester, MN, USA. Altrecht Mental Health Institute, Utrecht, The Netherlands. Araya, Inc, Tokyo, Japan. Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Intramural Research Program, National Institute on Aging, Baltimore, MD, USA. Division of Psychiatry, University of Edinburgh, Edinburgh, UK. Department of Clinical Science, University of Bergen, Bergen, Norway. Center for Genomic Medicine, Mass General Brigham, Boston, MA, USA. Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR , CNRS, Université de Bordeaux, Bordeaux, France. PPLS, University of Edinburgh, Edinburgh, UK. Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA. Department of Neurology, University of Washington, Seattle, WA, USA. Departments of Neurology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Department of Psychology, University of Edinburgh, Edinburgh, UK. Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale, INSERM U 'Trajectoires développementales Psychiatrie', Ecole Normale Supérieure Paris-Saclay, CNRS UMR , Université Paris Cité, Centre Borelli, Gif sur Yvette, France. School of Clinical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia. Institute of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Perugia, Italy. Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Institute of Neurogenomics, Helmholtz Munich, Neuherberg, Germany. Department of Psychiatry, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. MIND Center, Jackson, MS, USA. Statistics Genetics Group, Max Planck Institute of Psychiatry, Munich, Germany. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA. University Medical Center Groningen, Groningen, The Netherlands. Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany. Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Clinical Neuropsychology Section, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Université Libre de Bruxelles, Brussels, Belgium. Departments of Psychiatry and Neuroscience, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada. Hospital for Sick Children, Toronto, Ontario, Canada. Departments of Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Translational Psychiatry, Munich, Germany. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany. Department of Psychiatry and Neuroscience, Charité-Universitätsmedizin Berlin, Berlin, Germany. Departamento de Fisiología Médica y Biofísica, Instituto de Biomedicina de Sevilla (IBiS) HUVR/CSIC/Universidad de Sevilla/CIBERSAM, ISCIII, Sevilla, Spain. The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA. Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia. Institute of Molecular Biology and Biochemistry, Gottfried Schatz Center for Signaling, Metabolism and Aging, Medical University Graz, Graz, Austria. Department of Neurology, Medical University Graz Austria, Graz, Austria. Neuroscience Research Australia, Sydney, New South Wales, Australia. LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. The Hospital for Sick Children, Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada. Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK. Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. SAMRC Research Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Department of Genetics and UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Laboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA. Instituto de Física de Cantabria (CSIC-UC), Santander, Spain. Department of Biological Psychology and Netherlands Twin Register, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands. Department of Psychiatry, University Hospital Marqués de Valdecilla-IDIVAL, Santander, Spain. Department of Neurology, Max Planck Institute for Human, Cognitive and Brain Sciences, Leipzig, Germany. Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. University of California, San Francisco, San Francisco, CA, USA. Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden. Section on Social and Cognitive Developmental Neuroscience, National Institute of Mental Health, Bethesda, MD, USA. Framingham Heart Study, Chobanian and Avedisian Boston University School of Medicine, Boston, MA, USA. Brain and Mental Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. miguel.renteria@qimrberghofer.edu.au.
Abstract summary
Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson's disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.Authors & Co-authors: García-Marín Luis M LM Campos Adrian I AI Diaz-Torres Santiago S Rabinowitz Jill A JA Ceja Zuriel Z Mitchell Brittany L BL Grasby Katrina L KL Thorp Jackson G JG Agartz Ingrid I Alhusaini Saud S Ames David D Amouyel Philippe P Andreassen Ole A OA Arfanakis Konstantinos K Arias-Vasquez Alejandro A Armstrong Nicola J NJ Athanasiu Lavinia L Bastin Mark E ME Beiser Alexa S AS Bennett David A DA Bis Joshua C JC Boks Marco P M MPM Boomsma Dorret I DI Brodaty Henry H Brouwer Rachel M RM Buitelaar Jan K JK Burkhardt Ralph R Cahn Wiepke W Calhoun Vince D VD Carmichael Owen T OT Chakravarty Mallar M Chen Qiang Q Ching Christopher R K CRK Cichon Sven S Crespo-Facorro Benedicto B Crivello Fabrice F Dale Anders M AM Smith George Davey GD de Geus Eco J C EJC De Jager Philip L PL de Zubicaray Greig I GI Debette Stéphanie S DeCarli Charles C Depondt Chantal C Desrivières Sylvane S Djurovic Srdjan S Ehrlich Stefan S Erk Susanne S Espeseth Thomas T Fernández Guillén G Filippi Irina I Fisher Simon E SE Fleischman Debra A DA Fletcher Evan E Fornage Myriam M Forstner Andreas J AJ Francks Clyde C Franke Barbara B Ge Tian T Goldman Aaron L AL Grabe Hans J HJ Green Robert C RC Grimm Oliver O Groenewold Nynke A NA Gruber Oliver O Gudnason Vilmundur V Håberg Asta K AK Haukvik Unn K UK Heinz Andreas A Hibar Derrek P DP Hilal Saima S Himali Jayandra J JJ Ho Beng-Choon BC Hoehn David F DF Hoekstra Pieter J PJ Hofer Edith E Hoffmann Wolfgang W Holmes Avram J AJ Homuth Georg G Hosten Norbert N Ikram M Kamran MK Ipser Jonathan C JC Jack Clifford R CR Jahanshad Neda N Jönsson Erik G EG Kahn Rene S RS Kanai Ryota R Klein Marieke M Knol Maria J MJ Launer Lenore J LJ Lawrie Stephen M SM Hellard Stephanie Le SL Lee Phil H PH Lemaître Hervé H Li Shuo S Liewald David C M DCM Lin Honghuang H Longstreth W T WT Lopez Oscar L OL Luciano Michelle M Maillard Pauline P Marquand Andre F AF Martin Nicholas G NG Martinot Jean-Luc JL Mather Karen A KA Mattay Venkata S VS McMahon Katie L KL Mecocci Patrizia P Melle Ingrid I Meyer-Lindenberg Andreas A Mirza-Schreiber Nazanin N Milaneschi Yuri Y Mosley Thomas H TH Mühleisen Thomas W TW Müller-Myhsok Bertram B Maniega Susana Muñoz SM Nauck Matthias M Nho Kwangsik K Niessen Wiro J WJ Nöthen Markus M MM Nyquist Paul A PA Oosterlaan Jaap J Pandolfo Massimo M Paus Tomas T Pausova Zdenka Z Penninx Brenda W J H BWJH Pike G Bruce GB Psaty Bruce M BM Pütz Benno B Reppermund Simone S Rietschel Marcella D MD Risacher Shannon L SL Romanczuk-Seiferth Nina N Romero-Garcia Rafael R Roshchupkin Gennady V GV Rotter Jerome I JI Sachdev Perminder S PS Sämann Philipp G PG Saremi Arvin A Sargurupremraj Muralidharan M Saykin Andrew J AJ Schmaal Lianne L Schmidt Helena H Schmidt Reinhold R Schofield Peter R PR Scholz Markus M Schumann Gunter G Schwarz Emanuel E Shen Li L Shin Jean J Sisodiya Sanjay M SM Smith Albert V AV Smoller Jordan W JW Soininen Hilkka S HS Steen Vidar M VM Stein Dan J DJ Stein Jason L JL Thomopoulos Sophia I SI Toga Arthur W AW Tordesillas-Gutiérrez Diana D Trollor Julian N JN Valdes-Hernandez Maria C MC van T Ent Dennis D van Bokhoven Hans H van der Meer Dennis D van der Wee Nic J A NJA Vázquez-Bourgon Javier J Veltman Dick J DJ Vernooij Meike W MW Villringer Arno A Vinke Louis N LN Völzke Henry H Walter Henrik H Wardlaw Joanna M JM Weinberger Daniel R DR Weiner Michael W MW Wen Wei W Westlye Lars T LT Westman Eric E White Tonya T Witte A Veronica AV Wolf Christiane C Yang Jingyun J Zwiers Marcel P MP Ikram M Arfan MA Seshadri Sudha S Thompson Paul M PM Satizabal Claudia L CL Medland Sarah E SE Rentería Miguel E ME
Study Outcome
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Citations : Thompson, P. M. et al. ENIGMA and global neuroscience: a decade of large-scale studies of the brain in health and disease across more than 40 countries. Transl. Psychiatry 10, 1–28 (2020).Authors : 190
Identifiers
Doi : 10.1038/s41588-024-01951-zSSN : 1546-1718