Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs.

Journal: Human brain mapping

Volume: 43

Issue: 1

Year of Publication: 2022

Affiliated Institutions:  Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA. Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and University of Oslo, Oslo, Norway. Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, University of California Los Angeles, Los Angeles, California, USA. NORMENT, Institute of Clinical Psychiatry, University of Oslo, Oslo, Norway. Institute of Neuroscience and Medicine (INM-), Research Centre Jülich, Jülich, Germany. Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañon, IsSGM, Universidad Complutense, School of Medicine, Madrid, Spain. Mathematics and Statistics, Murdoch University, Perth, Western Australia, Australia. Centro Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain. Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands. Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State, Georgia Tech, Emory, Atlanta, Georgia, USA. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. Department of Forensic and Neurodevelopmental Sciences, The Sackler Institute for Translational Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom. HU Virgen del Rocio, IBIS, Universidad de Sevilla, CIBERSAM, Sevilla, Spain. MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom. Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, California, USA. Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. Faculty of Health, Queensland University of Technology (QUT), Brisbane, Queensland, Australia. Center for Neuroimaging, Genetics and Genomics, School of Psychology, NUI Galway, Galway, Ireland. LREN, Centre for Research in Neuroscience, Department of Neuroscience, University Hospital Lausanne and University Lausanne, Lausanne, Switzerland. MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis, Davis, California, USA. Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Dresden, Germany. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. Department of Psychology, University of Oslo, Oslo, Norway. Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands. Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, Massachusetts, USA. German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany. Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Medical Imaging Research Center, Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, USA. Department of Biomedicine, University of Bergen, Bergen, Norway. Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, USA. Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan. Personalized Healthcare Analytics, Genentech, Inc., South San Francisco, California, USA. Department of Psychology, Yale University, New Haven, Connecticut, USA. Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California, USA. School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway. Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Department of Psychology, Faculty of Social Sciences, University of Oslo, Oslo, Norway. Sainte Justine Hospital Research Center, University of Montreal, Montreal, QC, Canada. Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada. Translational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada. Bioinformatics Service, Nucleus, University of Salamanca, Salamanca, Spain. Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, USA. Department of Biomedicine, University of Basel, Basel, Switzerland. Center for Genetics and Genomics, Facultad de Medicina, Clinica Alemana Universidad del Desarrollo, Santiago, Chile. Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. Service de Troubles du Spectre de l'Autisme, Lausanne University Hospital, Lausanne, Switzerland. Department of Radiology and Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Neuroscience Research Australia, Sydney, New South Wales, Australia. Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom. Population Genomics, deCODE genetics/Amgen, Reykjavik, Iceland. SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom. Department of Psychiatry, The University of British Columbia, Vancouver, British Columbia, Canada. KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.

Abstract summary 

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.

Authors & Co-authors:  Sønderby Ida E IE Ching Christopher R K CRK Thomopoulos Sophia I SI van der Meer Dennis D Sun Daqiang D Villalon-Reina Julio E JE Agartz Ingrid I Amunts Katrin K Arango Celso C Armstrong Nicola J NJ Ayesa-Arriola Rosa R Bakker Geor G Bassett Anne S AS Boomsma Dorret I DI Bülow Robin R Butcher Nancy J NJ Calhoun Vince D VD Caspers Svenja S Chow Eva W C EWC Cichon Sven S Ciufolini Simone S Craig Michael C MC Crespo-Facorro Benedicto B Cunningham Adam C AC Dale Anders M AM Dazzan Paola P de Zubicaray Greig I GI Djurovic Srdjan S Doherty Joanne L JL Donohoe Gary G Draganski Bogdan B Durdle Courtney A CA Ehrlich Stefan S Emanuel Beverly S BS Espeseth Thomas T Fisher Simon E SE Ge Tian T Glahn David C DC Grabe Hans J HJ Gur Raquel E RE Gutman Boris A BA Haavik Jan J Håberg Asta K AK Hansen Laura A LA Hashimoto Ryota R Hibar Derrek P DP Holmes Avram J AJ Hottenga Jouke-Jan JJ Hulshoff Pol Hilleke E HE Jalbrzikowski Maria M Knowles Emma E M EEM Kushan Leila L Linden David E J DEJ Liu Jingyu J Lundervold Astri J AJ Martin-Brevet Sandra S Martínez Kenia K Mather Karen A KA Mathias Samuel R SR McDonald-McGinn Donna M DM McRae Allan F AF Medland Sarah E SE Moberget Torgeir T Modenato Claudia C Monereo Sánchez Jennifer J Moreau Clara A CA Mühleisen Thomas W TW Paus Tomas T Pausova Zdenka Z Prieto Carlos C Ragothaman Anjanibhargavi A Reinbold Céline S CS Reis Marques Tiago T Repetto Gabriela M GM Reymond Alexandre A Roalf David R DR Rodriguez-Herreros Borja B Rucker James J JJ Sachdev Perminder S PS Schmitt James E JE Schofield Peter R PR Silva Ana I AI Stefansson Hreinn H Stein Dan J DJ Tamnes Christian K CK Tordesillas-Gutiérrez Diana D Ulfarsson Magnus O MO Vajdi Ariana A van 't Ent Dennis D van den Bree Marianne B M MBM Vassos Evangelos E Vázquez-Bourgon Javier J Vila-Rodriguez Fidel F Walters G Bragi GB Wen Wei W Westlye Lars T LT Wittfeld Katharina K Zackai Elaine H EH Stefánsson Kári K Jacquemont Sebastien S Thompson Paul M PM Bearden Carrie E CE Andreassen Ole A OA

Study Outcome 

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Statistics
Citations :  Abdellaoui, A. , Ehli, E. A. , Hottenga, J. J. , Weber, Z. , Mbarek, H. , Willemsen, G. , … Boomsma, D. I. (2015). CNV concordance in 1,097 MZ twin pairs. Twin Research and Human Genetics, 18(1), 1–12. 10.1017/thg.2014.86
Authors :  105
Identifiers
Doi : 10.1002/hbm.25354
SSN : 1097-0193
Study Population
Male,Female
Mesh Terms
Brain
Other Terms
brain structural imaging;copy number variant;diffusion tensor imaging;evolution;genetics-first approach;neurodevelopmental disorders;psychiatric disorders
Study Design
Cross Sectional Study
Study Approach
Country of Study
Mali
Publication Country
United States