ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
Authors: Thompson Paul M. , Jahanshad Neda , Ching Christopher R. K. , Salminen Lauren E. , Thomopoulos Sophia I. , Bright Joanna , Baune Bernhard T. , Bertolín Sara , Bralten Janita , Bruin Willem B. , Bülow Robin , Chen Jian , Chye Yann , Dannlowski Udo , de Kovel Carolien G. F. , Donohoe Gary , Eyler Lisa T. , Faraone Stephen V. , Favre Pauline , Filippi Courtney A. , Frodl Thomas , Garijo Daniel , Gil Yolanda , Grabe Hans J. , Grasby Katrina L. , Hajek Tomas , Han Laura K. M. , Hatton Sean N. , Hilbert Kevin , Ho Tiffany C. , Holleran Laurena , Homuth Georg , Hosten Norbert , Houenou Josselin , Ivanov Iliyan , Jia Tianye , Kelly Sinead , Klein Marieke , Kwon Jun Soo , Laansma Max A. , Leerssen Jeanne , Lueken Ulrike , Nunes Abraham , Neill Joseph O’ , Opel Nils , Piras Fabrizio , Piras Federica , Postema Merel C. , Pozzi Elena , Shatokhina Natalia , Soriano-Mas Carles , Spalletta Gianfranco , Sun Daqiang , Teumer Alexander , Tilot Amanda K. , Tozzi Leonardo , van der Merwe Celia , Van Someren Eus J. W. , van Wingen Guido A. , Völzke Henry , Walton Esther , Wang Lei , Winkler Anderson M. , Wittfeld Katharina , Wright Margaret J. , Yun Je-Yeon , Zhang Guohao , Zhang-James Yanli , Adhikari Bhim M. , Agartz Ingrid , Aghajani Moji , Aleman André , Althoff Robert R. , Altmann Andre , Andreassen Ole A. , Baron David A. , Bartnik-Olson Brenda L. , Marie Bas-Hoogendam Janna , Baskin-Sommers Arielle R. , Bearden Carrie E. , Berner Laura A. , Boedhoe Premika S. W. , Brouwer Rachel M. , Buitelaar Jan K. , Caeyenberghs Karen , Cecil Charlotte A. M. , Cohen Ronald A. , Cole James H. , Conrod Patricia J. , De Brito Stephane A. , de Zwarte Sonja M. C. , Dennis Emily L. , Desrivieres Sylvane , Dima Danai , Ehrlich Stefan , Esopenko Carrie , Fairchild Graeme , Fisher Simon E. , Fouche Jean-Paul , Francks Clyde , Frangou Sophia , Franke Barbara , Garavan Hugh P. , Glahn David C. , Groenewold Nynke A. , Gurholt Tiril P. , Gutman Boris A. , Hahn Tim , Harding Ian H. , Hernaus Dennis , Hibar Derrek P. , Hillary Frank G. , Hoogman Martine , Hulshoff Pol Hilleke E. , Jalbrzikowski Maria , Karkashadze George A. , Klapwijk Eduard T. , Knickmeyer Rebecca C. , Kochunov Peter , Koerte Inga K. , Kong Xiang-Zhen , Liew Sook-Lei , Lin Alexander P. , Logue Mark W. , Luders Eileen , Macciardi Fabio , Mackey Scott , Mayer Andrew R. , McDonald Carrie R. , McMahon Agnes B. , Medland Sarah E. , Modinos Gemma , Morey Rajendra A. , Mueller Sven C. , Mukherjee Pratik , Namazova-Baranova Leyla , Nir Talia M. , Olsen Alexander , Paschou Peristera , Pine Daniel S. , Pizzagalli Fabrizio , Rentería Miguel E. , Rohrer Jonathan D. , Sämann Philipp G. , Schmaal Lianne , Schumann Gunter , Shiroishi Mark S. , Sisodiya Sanjay M. , Smit Dirk J. A. , Sønderby Ida E. , Stein Dan J. , Stein Jason L. , Tahmasian Masoud , Tate David F. , Turner Jessica A. , van den Heuvel Odile A. , van der Wee Nic J. A. , van der Werf Ysbrand D. , van Erp Theo G. M. , van Haren Neeltje E. M. , van Rooij Daan , van Velzen Laura S. , Veer Ilya M. , Veltman Dick J. , Villalon-Reina Julio E. , Walter Henrik , Whelan Christopher D. , Wilde Elisabeth A. , Zarei Mojtaba , Zelman Vladimir ,   for the ENIGMA Consortium
Published: March 2020

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.