This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA

APHP Mondor University Hospitals School of Medicine DMU Impact Psychiatry Department Créteil France

Biological Sciences Purdue University West Lafayette IN USA

Biomedical Engineering Illinois Institute of Technology Chicago IL USA

Biomedical Genetics Boston University School of Medicine Boston MA USA

Biometris Wageningen University and Research Wageningen The Netherlands

Brain and Mind Centre University of Sydney Sydney Australia

CBRAIN Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy Ludwig Maximilians Universität München Munich Germany

Center for Clinical Spectroscopy Brigham and Women's Hospital Boston MA USA

Center for Cognitive Aging and Memory University of Florida Gainesville FL USA

Center for Multimodal Imaging and Genetics University of California San Diego La Jolla CA USA

Center for the Neurobiology of Learning and Memory University of California Irvine Irvine CA USA

Centre for Advanced Imaging University of Queensland Brisbane QLD Australia

Centre for Medical Image Computing Department of Computer Science University College London London UK

Centre for Medical Image Computing Department of Medical Physics and Biomedical Engineering University College London London UK

Centre for Population Neuroscience and Precision Medicine MRC SGDP Centre Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Centre for Youth Mental Health The University of Melbourne Melbourne VIC Australia

Chalfont Centre for Epilepsy Chalfont St Peter UK

Chan Division of Occupational Science and Occupational Therapy Los Angeles CA USA

Child and Adolescent Psychiatry University of California Los Angeles Los Angeles CA USA

CIBERSAM G17 Madrid Spain

Clinical and Health Psychology Gainesville FL USA

Clinical Translational Neuroscience Laboratory Department of Psychiatry and Human Behavior University of California Irvine Irvine CA USA

Cognitive Neuroscience Unit School of Psychology Deakin University Burwood VIC Australia

Dementia Research Centre Institute of Neurology University College London London UK

Department of Anatomy and Neurosciences Amsterdam UMC Location VUmc Amsterdam Neuroscience Amsterdam The Netherlands

Department of Brain and Cognitive Sciences Seoul National University College of Natural Sciences Seoul Republic of Korea

Department of Child and Adolescent Psychiatry Psychology Erasmus Medical Centre Rotterdam The Netherlands

Department of Clinical and Experimental Epilepsy University College London London UK

Department of Clinical Neuroscience Centre for Psychiatric Research Karolinska Institutet Stockholm Sweden

Department of Cognitive Neuroscience Donders Institute for Brain Cognition and Behaviour Radboud University Medical Center Nijmegen The Netherlands

Department of Computer Science and Electrical Engineering University of Maryland Baltimore County MD USA

Department of Computer Science and Engineering The Ohio State University Columbus OH USA

Department of Computer Science University of Southern California Los Angeles CA USA

Department of Epidemiology Erasmus Medical Centre Rotterdam The Netherlands

Department of Genetics and Computational Biology QIMR Berghofer Medical Research Institute Brisbane QLD Australia

Department of Genetics and UNC Neuroscience Center University of North Carolina at Chapel Hill Chapel Hill NC USA

Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands

Department of Medical Genetics Oslo University Hospital Oslo Norway

Department of Mental Health Veterans Affairs Greater Los Angeles Healthcare System Los Angeles CA USA

Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology London UK

Department of Neuroimaging Institute of Psychology Psychiatry and Neurosciences King's College London London UK

Department of Neurology TBI and Concussion Center Salt Lake City UT USA

Department of Neurology University of Utah Salt Lake City UT USA

Department of Pediatrics Michigan State University East Lansing MI USA

Department of Pediatrics Russian National Research Medical University MoH RF Moscow Russian Federation

Department of Personality Psychological Assessment and Treatment University of Deusto Bilbao Spain

Department of Physical Medicine and Rehabilitation Baylor College of Medicine Houston TX USA

Department of Physical Medicine and Rehabilitation St Olavs Hospital Trondheim University Hospital Trondheim Norway

Department of Psychiatric Research Diakonhjemmet Hospital Oslo Norway

Department of Psychiatry Amsterdam UMC Location VUmc Amsterdam Neuroscience Amsterdam The Netherlands

Department of Psychiatry Amsterdam UMC University of Amsterdam Amsterdam Neuroscience Amsterdam The Netherlands

Department of Psychiatry Amsterdam University Medical Centers VU University Medical Center GGZ inGeest Amsterdam Neuroscience Amsterdam The Netherlands

Department of Psychiatry and Behavioral Sciences Baylor College of Medicine Houston TX USA

Department of Psychiatry and Behavioral Sciences Stanford University Stanford CA USA

Department of Psychiatry and Behavioral Sciences SUNY Upstate Medical University Syracuse NY USA

Department of Psychiatry and Biobehavioral Sciences Semel Institute for Neuroscience and Human Behavior University of California Los Angeles Los Angeles CA USA

Department of Psychiatry and Human Behavior University of California Irvine Irvine CA USA

Department of Psychiatry and Mental Health University of Cape Town Cape Town South Africa

Department of Psychiatry and Neuropsychology School for Mental Health and Neuroscience Maastricht University Maastricht The Netherlands

Department of Psychiatry and Neuroscience Institute SA MRC Unit on Risk and Resilience in Mental Disorders Cape Town South Africa

Department of Psychiatry and Psychotherapy Charite Humboldt University Berlin Germany

Department of Psychiatry and Psychotherapy Otto von Guericke University Magdeburg Magdeburg Germany

Department of Psychiatry and Psychotherapy University Medicine Greifswald Greifswald Germany

Department of Psychiatry and Weill Institute for Neurosciences University of California San Francisco San Francisco CA USA

Department of Psychiatry Bellvitge University Hospital Bellvitge Biomedical Research Institute IDIBELL Barcelona Spain

Department of Psychiatry Beth Israel Deaconess Medical Center Harvard Medical School Boston MA USA

Department of Psychiatry Boston Children's Hospital and Harvard Medical School Boston MA USA

Department of Psychiatry Boston University School of Medicine Boston MA USA

Department of Psychiatry Brigham and Women's Hospital Boston MA USA

Department of Psychiatry Dalhousie University Halifax NS Canada

Department of Psychiatry Duke University School of Medicine Durham NC USA

Department of Psychiatry Icahn School of Medicine at Mount Sinai New York NY USA

Department of Psychiatry Leiden University Medical Center Leiden The Netherlands

Department of Psychiatry Radboud University Medical Center Nijmegen The Netherlands

Department of Psychiatry Seoul National University College of Medicine Seoul Republic of Korea

Department of Psychiatry The University of Melbourne Melbourne VIC Australia

Department of Psychiatry Trinity College Dublin Dublin Ireland

Department of Psychiatry UMC Brain Center University Medical Center Utrecht Utrecht University Utrecht The Netherlands

Department of Psychiatry University of California San Diego La Jolla CA USA

Department of Psychiatry University of Maryland School of Medicine Baltimore MD USA

Department of Psychiatry University of Münster Münster Germany

Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill NC USA

Department of Psychiatry University of Pittsburgh Pittsburgh PA USA

Department of Psychiatry University of Vermont Burlington VT USA

Department of Psychobiology and Methodology in Health Sciences Universitat Autònoma de Barcelona Barcelona Spain

Department of Psychology Humboldt Universität zu Berlin Berlin Germany

Department of Psychology Norwegian University of Science and Technology Trondheim Norway

Department of Psychology Penn State University University Park PA USA

Department of Psychology School of Arts and Social Sciences City University of London London UK

Department of Psychology University of Bath Bath UK

Department of Psychology University of California Los Angeles CA USA

Department of Psychology Yale University New Haven CT USA

Department of Psychosis Studies Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Department of Radiology Keck School of Medicine of USC University of Southern California Los Angeles CA USA

Department of Radiology Loma Linda University Medical Center Loma Linda CA USA

Department of Rehabilitation and Movement Sciences School of Health Professions Rutgers Biomedical Health Sciences Newark NJ USA

Department of Research and Innovation GGZ InGeest Amsterdam The Netherlands

Department of Sleep and Cognition Netherlands Institute for Neuroscience Amsterdam The Netherlands

Departments of Psychiatry and of Neuroscience and Physiology SUNY Upstate Medical University Syracuse NY USA

Desert Pacific Mental Illness Research Education and Clinical Center VA San Diego Healthcare System San Diego CA USA

Division of Mental Health and Addiction Oslo University Hospital Oslo Norway

Division of Mind and Brain Research Department of Psychiatry and Psychotherapy CCM Charité Universitätsmedizin Berlin corporate member of Freie Universität Berlin Humboldt Universität zu Berlin and Berlin Institute of Health Berlin Germany

Division of Psychological and Social Medicine and Developmental Neurosciences Faculty of Medicine TU Dresden Dresden Germany

Donders Centre for Cognitive Neuroimaging Radboud University Medical Centre Nijmegen The Netherlands

Donders Institute for Brain Cognition and Behaviour Radboud University Nijmegen The Netherlands

Experimental Clinical and Health Psychology Ghent University Ghent Belgium

Faculty of Computer Science Dalhousie University Halifax NS Canada

Genentech Inc South San Francisco CA USA

German Center for Neurodegenerative Diseases Magdeburg Germany

German Center for Neurodegenerative Diseases Site Rostock Greifswald Greifswald Germany

German Centre for Cardiovascular Research Partner Site Greifswald Greifswald Germany

Harvard Medical School Boston MA USA

Icahn School of Medicine at Mount Sinai New York NY USA

Imaging Genetics Center Mark and Mary Stevens Neuroimaging and Informatics Institute Keck School of Medicine University of Southern California Marina del Rey CA USA

Information Sciences Institute University of Southern California Marina del Rey CA USA

INSERM Unit 955 Team 15 'Translational Psychiatry' Créteil France

Institute for Community Medicine University Medicine Greifswald Greifswald Germany

Institute for Diagnostic Radiology and Neuroradiology University Medicine Greifswald Greifswald Germany

Institute for Information Transmission Problems Kharkevich Institute Moscow Russian Federation

Institute for Quantitative Health Science and Engineering East Lansing MI USA

Institute of Medical Science and Technology Shahid Beheshti University Tehran 1 R Iran

Institute of Psychology Leiden University Leiden The Netherlands

Institute of Science and Technology for Brain Inspired Intelligence Fudan University Shanghai China

Interfaculty Institute for Genetics and Functional Genomics University Medicine Greifswald Greifswald Germany

Keck School of Medicine University of Southern California Los Angeles CA USA

Laboratory of Neuro Imaging Mark and Mary Stevens Neuroimaging and Informatics Institute Keck School of Medicine University of Southern California Los Angeles CA USA

Laboratory of Neuropsychiatry IRCCS Santa Lucia Foundation Rome Italy

Language and Genetics Department Max Planck Institute for Psycholinguistics Nijmegen The Netherlands

Leiden Institute for Brain and Cognition Leiden The Netherlands

Max Planck Institute of Psychiatry Munich Germany

Melbourne Neuropsychiatry Centre Department of Psychiatry The University of Melbourne Melbourne VIC Australia

Mental Illness Research Education and Clinical Center Durham VA Medical Center Durham NC USA

Mind Research Network Albuquerque NM USA

Missouri Institute of Mental Health Berkeley MO USA

MOE Key Laboratory of Computational Neuroscience and Brain Inspired Intelligence Fudan University Shanghai China

Molecular and Cellular Therapeutics Royal College of Surgeons in Ireland Dublin Ireland

National Center for PTSD at Boston VA Healthcare System Boston MA USA

National Institute of Mental Health Intramural Research Program Bethesda MD USA

National Institute of Mental Health Klecany Czech Republic

National Institute of Mental Health National of Health Bethesda MD USA

NeuroSpin UNIACT Lab Psychiatry Team CEA Saclay Gif Sur Yvette France

Norwegian Centre for Mental Disorders Research Division of Mental Health and Addiction Institute of Clinical Medicine University of Oslo Oslo Norway

Olin Neuropsychiatric Research Center Institute of Living Hartford CT USA

Orygen The National Centre of Excellence in Youth Mental Health Melbourne VIC Australia

Provost and Senior Vice President Western University of Health Sciences Pomona CA USA

Psychiatric Genetics QIMR Berghofer Medical Research Institute Brisbane QLD Australia

Psychiatry and Behavioral Sciences Northwestern University Feinberg School of Medicine Chicago IL USA

Psychiatry and Integrative Neurophysiology VU University Amsterdam UMC Amsterdam The Netherlands

Psychiatry Neuroimaging Laboratory Brigham and Women's Hospital Harvard Medical School Boston MA USA

Psychiatry Pediatrics and Psychological Sciences University of Vermont Burlington VT USA

Psychiatry San Diego CA USA

Psychology Department and Neuroscience Institute Georgia State University Atlanta GA USA

Queensland Brain Institute University of Queensland Brisbane QLD Australia

Radiology and Biomedical Imaging San Francisco CA USA

Radiology Northwestern University Feinberg School of Medicine Chicago IL USA

Research and Early Development Biogen Inc Cambridge MA USA

Research and Scientific Institute of Pediatrics and Child Health CCH RAS Ministry of Science and Higher Education Moscow Russian Federation

School of Psychology and Centre for Human Brain Health University of Birmingham Birmingham UK

School of Psychology University of Auckland Auckland New Zealand

Seoul National University Hospital Seoul Republic of Korea

Skolkovo Institute of Science and Technology Moscow Russian Federation

Social Genetic and Developmental Psychiatry Centre Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Social Life and Engineering Sciences Imaging Center University Park PA USA

Stanley Center for Psychiatric Research The Broad Institute Cambridge MA USA

Stevens Neuroimaging and Informatics Institute Keck School of Medicine University of Southern California Los Angeles CA USA

SU UCT MRC Unit on Risk and Resilience in Mental Disorders University of Stellenbosch Stellenbosch South Africa

The Center for Neuroimaging and Cognitive Genomics School of Psychology National University of Ireland Galway Ireland

The Florey Institute of Neuroscience and Mental Health The University of Melbourne Melbourne VIC Australia

The Kavli Foundation Los Angeles CA USA

Turner Institute for Brain and Mental Health and School of Psychological Sciences Monash University Melbourne VIC Australia

Turner Institute for Brain and Mental Health School of Psychological Sciences Monash University Clayton VIC Australia

Universite de Montreal Centre de Recherche CHU Ste Justine Montreal QC Canada

University of British Columbia Vancouver Canada

University of Groningen University Medical Center Groningen Groningen The Netherlands

VA Salt Lake City Healthcare System Salt Lake City UT USA

Yeongeon Student Support Center Seoul National University College of Medicine Seoul Republic of Korea

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White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals

Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders-ENIGMA study in people with bipolar disorders and obesity

Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study

Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants

Bridging Big Data: Procedures for Combining Non-equivalent Cognitive Measures from the ENIGMA Consortium

Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals

Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals

What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group

Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals

Neuroimaging in Functional Neurological Disorder: State of the Field and Research Agenda

JuSpace: A tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps

Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders