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Front Neuroinform. 2019 Jan 8;12:102. doi: 10.3389/fninf.2018.00102. eCollection 2018.

An Empirical Comparison of Meta- and Mega-Analysis With Data From the ENIGMA Obsessive-Compulsive Disorder Working Group.

Author information

1
Department of Psychiatry, Amsterdam University Medical Centers (UMC), Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, Netherlands.
2
Department of Anatomy and Neurosciences, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, Netherlands.
3
Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
4
Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia.
5
Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
6
Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
7
Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
8
Centro de Investigación Biomèdica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
9
Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
10
Department of Psychiatry, Faculty of Medicine, The Centre for Addiction and Mental Health, The Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Campbell Family Mental Health Research Institute, University of Toronto, Toronto, ON, Canada.
11
The Hospital for Sick Children, Centre for Brain and Mental Health, Toronto, ON, Canada.
12
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States.
13
Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
14
Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
15
Departamento de Psiquiatria, Faculdade de Medicina, Instituto de Psiquiatria, Universidade de São Paulo, São Paulo, Brazil.
16
Division of Neuroscience, Psychiatry and Clinical Psychobiology, Scientific Institute Ospedale San Raffaele, Milan, Italy.
17
Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
18
Obsessive-Compulsive Disorder (OCD) Clinic Department of Psychiatry National Institute of Mental Health and Neurosciences, Bangalore, India.
19
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
20
Magnetic Resonance Image Core Facility, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.
21
Department of Child and Adolescent Psychiatry and Psychology, Hospital Clínic Universitari, Institute of Neurosciences, Barcelona, Spain.
22
Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China.
23
Institute of Human Behavioral Medicine, SNU-MRC, Seoul, South Korea.
24
Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
25
Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
26
Department of Psychiatry, Amsterdam Neuroscience, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
27
Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands.
28
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, United States.
29
Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
30
MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa.
31
Imaging Genetics Center, Keck School of Medicine of the University of Southern California, Mark and Mary Stevens Neuroimaging and Informatics Institute, Marina del Rey, CA, United States.
32
Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine, Shanghai, China.
33
De Bascule, Academic Center for Child and Adolescent Psychiatry, Amsterdam, Netherlands.
34
Department of Child and Adolescent Psychiatry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
35
Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, South Korea.
36
Department of Psychiatry, Oxford University, Oxford, United Kingdom.
37
Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
38
TUM-Neuroimaging Center (TUM-NIC) of Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
39
Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.
40
Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, South Korea.
41
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
42
Department of Medicine, University of Barcelona, Barcelona, Spain.
43
SU/UCT MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa.
44
Columbia University Medical College, Columbia University, New York, NY, United States.
45
The New York State Psychiatric Institute, New York, NY, United States.
46
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
47
Mood Disorders Clinic, St. Joseph's HealthCare, Hamilton, ON, Canada.
48
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
49
ATR Brain Information Communication Research Laboratory Group, Kyoto, Japan.
50
Center for Mathematics, Computing and Cognition, Universidade Federal do ABC, Santo Andre, Brazil.
51
Center for OCD and Related Disorders, New York State Psychiatric Institute, New York, NY, United States.
52
Anxiety Treatment and Research Center, St. Joseph's HealthCare, Hamilton, ON, Canada.
53
Department of Psychobiology and Methodology of Health Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
54
Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States.
55
Yale University School of Medicine, New Haven, CT, United States.
56
Clinical Neuroscience and Development Laboratory, Olin Neuropsychiatry Research Center, Hartford, CT, United States.
57
Icahn School of Medicine at Mount Sinai, New York, NY, United States.
58
James J. Peters VA Medical Center, Bronx, NY, United States.
59
Institute of Living/Hartford Hospital, Hartford, CT, United States.
60
Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China.

Abstract

Objective: Brain imaging communities focusing on different diseases have increasingly started to collaborate and to pool data to perform well-powered meta- and mega-analyses. Some methodologists claim that a one-stage individual-participant data (IPD) mega-analysis can be superior to a two-stage aggregated data meta-analysis, since more detailed computations can be performed in a mega-analysis. Before definitive conclusions regarding the performance of either method can be drawn, it is necessary to critically evaluate the methodology of, and results obtained by, meta- and mega-analyses. Methods: Here, we compare the inverse variance weighted random-effect meta-analysis model with a multiple linear regression mega-analysis model, as well as with a linear mixed-effects random-intercept mega-analysis model, using data from 38 cohorts including 3,665 participants of the ENIGMA-OCD consortium. We assessed the effect sizes and standard errors, and the fit of the models, to evaluate the performance of the different methods. Results: The mega-analytical models showed lower standard errors and narrower confidence intervals than the meta-analysis. Similar standard errors and confidence intervals were found for the linear regression and linear mixed-effects random-intercept models. Moreover, the linear mixed-effects random-intercept models showed better fit indices compared to linear regression mega-analytical models. Conclusions: Our findings indicate that results obtained by meta- and mega-analysis differ, in favor of the latter. In multi-center studies with a moderate amount of variation between cohorts, a linear mixed-effects random-intercept mega-analytical framework appears to be the better approach to investigate structural neuroimaging data.

KEYWORDS:

IPD meta-analysis; MRI; linear mixed-effect models; mega-analysis; neuroimaging

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