ENIGMA and Global Neuroscience: A Decade of Large-Scale Studies of the Brain in Health and Disease across more than 40 Countries

Abstract

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics throughMeta Analysis) Consortium, a global alliance of over 1,400 scientists across 43 countries, studying the humanbrain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicatedgenetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), poolingworldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, andgenetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normalvariation due to sex and gender differences, or development and aging; still other WGs develop methodologicalpipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodalMRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studiesto date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance usedisorders, 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, antisocialpersonality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade ofENIGMA’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 androbustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes acrossdiverse samples and associated genetic, environmental, demographic, cognitive and psychosocial factors.