A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

CIBERSAM Madrid Spain; Bipolar and depressive disorders Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona Spain; Barcelona Bipolar Disorders Program Institute of Neurosciences Hospital Clinic de Barcelona Barcelona Spain; University of Barcelona Barcelona Spain

CIBERSAM Madrid Spain; Department of Child and Adolescent Psychiatry Institute of Psychiatry and Mental Health Hospital General Universitario Gregorio Marañón Madrid Spain; Instituto de Investigación Sanitaria Gregorio Marañón Madrid Spain

CIBERSAM Madrid Spain; Department of Child and Adolescent Psychiatry Institute of Psychiatry and Mental Health Hospital General Universitario Gregorio Marañón Madrid Spain; Instituto de Investigación Sanitaria Gregorio Marañón Madrid Spain; School of Medicine Universidad Complutense Madrid Spain

CIBERSAM Madrid Spain; FIDMAG Germanes Hospitalàries Research Foundation Barcelona Spain

CIBERSAM Madrid Spain; FIDMAG Germanes Hospitalàries Research Foundation Barcelona Spain; Department of Radiology Centre Hospitalier Universitaire Vaudois École Polytechnique Fédérale de Lausanne Lausanne Switzerland

CIBERSAM Madrid Spain; FIDMAG Germanes Hospitalàries Research Foundation Barcelona Spain; School of Medicine Universitat Internacional de Catalunya Barcelona Spain

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 309 Qureshey Research Lab Irvine CA 92697 USA

Department of Basic Medical Science Neuroscience and Sense Organs University of Bari 'Aldo Moro' Bari Italy

Department of Mental Health Johns Hopkins Bloomberg School of Public Health Baltimore MD USA; Departments of Psychiatry Neuroscience and Biomedical Engineering Johns Hopkins School of Medicine Baltimore MD USA

Department of Neuropsychiatry University of Toyama Graduate School of Medicine and Pharmaceutical Sciences Toyama Japan; Department of Mental Health Johns Hopkins Bloomberg School of Public Health Baltimore MD 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 Western Cape South Africa; Department of Child and Adolescent Psychiatry Technische Universität Dresden Dresden Germany

Department of Psychiatry and Mental Health University of Cape Town Cape Town Western Cape South Africa; Neuroscience Institute University of Cape Town Cape Town Western Cape South Africa

Department of Psychiatry and Mental Health University of Cape Town Cape Town Western Cape South Africa; Valkenburg Hospital Observatory Cape Town Western Cape South Africa

Department of Psychiatry and Neuropsychology Maastricht University Maastricht The Netherlands

Department of Psychiatry and Psychotherapy Philipps University Marburg Marburg Germany

Department of Psychiatry Psychotherapy and Psychosomatics Psychiatric Hospital University of Zurich Zurich Switzerland; Montreal Neurological Institute McGill University Montreal Canada

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

Department of Psychiatry University of Basel Basel Switzerland; Department of Psychiatry and Psychotherapy University Lübeck Germany

Department of Psychiatry University of Münster Münster Germany

Department of Psychiatry University of Oxford Oxford UK

Department of Psychiatry University of Pennsylvania Philadelphia PA USA

Departments of Psychiatry Johns Hopkins School of Medicine Baltimore MD USA

Dept of Psychiatry Psychosomatic Medicine and Psychotherapy Goethe University Frankfurt Frankfurt Germany

Georgia State University Atlanta GA USA

Health Behaviour Research Group School of Medicine and Public Health University of Newcastle Newcastle NSW Australia

Imaging Genetics Center Department of Neurology University of Southern California Los Angeles CA USA

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

Imaging of Mood and Anxiety Related Disorders Barcelona Spain

Imaging of Mood and Anxiety Related Disorders Barcelona Spain; CIBERSAM Madrid Spain; FIDMAG Germanes Hospitalàries Research Foundation Barcelona Spain

Imaging of Mood and Anxiety Related Disorders Barcelona Spain; CIBERSAM Madrid Spain; FIDMAG Germanes Hospitalàries Research Foundation Barcelona Spain; Department of Psychiatry and Forensic Medicine School of Medicine Autonomous University of Barcelona Barcelona Spain

Imaging of Mood and Anxiety Related Disorders Lab Institute of Psychiatry Psychology and Neuroscience King's College London London UK; Department of Clinical Neuroscience Stockholm Health Care Services Stockholm County Council Karolinska Institutet Stockholm Sweden

IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo Italy; Department of Basic Medical Science Neuroscience and Sense Organs University of Bari 'Aldo Moro' Bari Italy

Laboratory of Neuropsychiatry Department of Clinical and Behavioral Neurology IRCCS Santa Lucia Foundation Rome Italy

Laboratory of Neuropsychiatry Department of Clinical and Behavioral Neurology IRCCS Santa Lucia Foundation Rome Italy; Division of Neuropsychiatry Menninger Department of Psychiatry and Behavioral Sciences Baylor College of Medicine Houston TX USA

Maryland Psychiatric Research Center University of Maryland School of Medicine Baltimore MD USA

Melbourne Neuropsychiatry Centre Dept of Psychiatry University of Melbourne Melbourne VIC Australia

Melbourne Neuropsychiatry Centre Dept of Psychiatry University of Melbourne Melbourne VIC Australia; North Western Mental Health Melbourne Health Melbourne VIC Australia

Mental Health Research Center Moscow Russia

Murdoch Children's Research Institute Melbourne VIC Australia; The University of Melbourne Australia

National Institute of Mental Health Klecany Czech Republic; Department of Psychiatry and Clinical Psychology 3rd Faculty of Medicine Charles University Prague Czech Republic

National Institute of Mental Health Klecany Czech Republic; Institute of Computer Science Czech Academy of Sciences Prague Czech Republic; Faculty of Electrical Engineering Czech Technical University Prague Prague Czech Republic

National Institute of Mental Health Klecany Czech Republic; MR Unit Department of Diagnostic and Interventional Radiology Institute for Clinical and Experimental Medicine Prague Czech Republic

Penn Statistics in Imaging and Visualization Center Department of Biostatistics Epidemiology and Informatics University of Pennsylvania Philadelphia PA USA; Center for Biomedical Image Computing and Analytics University of Pennsylvania Philadelphia PA USA

Psychiatry Research Center Beijing Huilongguan Hospital Beijing China

Queensland Brain Institute The University of Queensland Brisbane QLD Australia; Queensland Centre for Mental Health Research The University of Queensland Brisbane QLD Australia

Research Group in Psychiatry GIPSI Department of Psychiatry Faculty of Medicine Universidad de Antioquia Medellín Antioquia Colombia

Research Group in Psychiatry GIPSI Department of Psychiatry Faculty of Medicine Universidad de Antioquia Medellín Antioquia Colombia; Mood Disorders Program Hospital Universitario San Vicente Fundación Medellin Colombia

SAMRC Unit on Risk and Resilience in Mental Disorders Dept of Psychiatry and Neuroscience Institute University of Cape Town Cape Town Western Province South Africa

School of Medical Sciences University of New South Wales Sydney NSW Australia; Neuroscience Research Australia Sydney NSW Australia

School of Psychiatry University of New South Wales Sydney NSW Australia; Center for Biomedical Image Computing and Analytics University of Pennsylvania Philadelphia PA USA

School of Psychiatry University of New South Wales Sydney NSW Australia; Neuroscience Research Australia Sydney NSW Australia

School of Psychiatry University of New South Wales Sydney NSW Australia; Neuroscience Research Australia Sydney NSW Australia; Department of Neuroscience and Physiology Upstate Medical University Syracuse Newyork NY USA

School of Psychiatry University of New South Wales Sydney NSW Australia; Neuroscience Research Australia Sydney NSW Australia; University of New Mexico Albuquerque NM USA

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

Technische Universität Dresden Faculty of Medicine Division of Psychological and Social Medicine Dresden Germany

Tri institutional Center for Translational Research in Neuroimaging and Data Science Georgia State Georgia Tech Emory Atlanta GA USA

University of Barcelona Barcelona Spain; Center of Neuroimmunology Laboratory of Advanced Imaging in Neuroimmunological Diseases Hospital Clinic de Barcelona Barcelona Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona Spain

University of Newcastle Newcastle NSW Australia

University of Newcastle Newcastle NSW Australia; Hunter Medical Research Institute Newcastle NSW Australia

University of Stellenbosch Cape Town Western Province South Africa

West Region and Research Division 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

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Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium

Cortical morphology in patients with the deficit and non-deficit syndrome of schizophrenia: a worldwide meta- and mega-analyses

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

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

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NTR
NTR5094