Mega-analysis methods in ENIGMA: The experience of the generalized anxiety disorder working group

André Zugman, Anita Harrewijn, Elise M. Cardinale, Hannah Zwiebel, Gabrielle F. Freitag, Katy E. Werwath, Janna M. Bas-Hoogendam, Nynke A. Groenewold, Moji Aghajani, Kevin Hilbert, Narcis Cardoner, Daniel Porta-Casteràs, Savannah Gosnell, Ramiro Salas, Karina S. Blair, James R. Blair, Mira Z. Hammoud, Mohammed Milad, Katie Burkhouse, K. Luan PhanHeidi K. Schroeder, Jeffrey R. Strawn, Katja Beesdo-Baum, Sophia I. Thomopoulos, Hans J. Grabe, Sandra Van der Auwera, Katharina Wittfeld, Jared A. Nielsen, Randy Buckner, Jordan W. Smoller, Benson Mwangi, Jair C. Soares, Mon Ju Wu, Giovana B. Zunta-Soares, Andrea P. Jackowski, Pedro M. Pan, Giovanni A. Salum, Michal Assaf, Gretchen J. Diefenbach, Paolo Brambilla, Eleonora Maggioni, David Hofmann, Thomas Straube, Carmen Andreescu, Rachel Berta, Erica Tamburo, Rebecca Price, Gisele G. Manfro, Hugo D. Critchley, Elena Makovac, Matteo Mancini, Frances Meeten, Cristina Ottaviani, Federica Agosta, Elisa Canu, Camilla Cividini, Massimo Filippi, Milutin Kostić, Ana Munjiza, Courtney A. Filippi, Ellen Leibenluft, Bianca A.V. Alberton, Nicholas L. Balderston, Monique Ernst, Christian Grillon, Lilianne R. Mujica-Parodi, Helena van Nieuwenhuizen, Gregory A. Fonzo, Martin P. Paulus, Murray B. Stein, Raquel E. Gur, Ruben C. Gur, Antonia N. Kaczkurkin, Bart Larsen, Theodore D. Satterthwaite, Jennifer Harper, Michael Myers, Michael T. Perino, Qiongru Yu, Chad M. Sylvester, Dick J. Veltman, Ulrike Lueken, Nic J.A. Van der Wee, Dan J. Stein, Neda Jahanshad, Paul M. Thompson, Daniel S. Pine, Anderson M. Winkler

Research output: Contribution to journalReview articlepeer-review

39 Scopus citations


The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

Original languageEnglish (US)
Pages (from-to)255-277
Number of pages23
JournalHuman Brain Mapping
Issue number1
StatePublished - Jan 2022


  • data sharing
  • generalized anxiety disorder
  • mega-analyses
  • meta-analyses
  • neuroimaging

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology


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