ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

for the ENIGMA Consortium

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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.

Original languageEnglish
Article number100
JournalTranslational Psychiatry
Issue number1
Publication statusPublished - 1 Dec 2020


The work reported here was supported in part by many public and private agencies across the world. Individual authors’ funding is listed in Supplementary Appendix B. Core funding for ENIGMA was provided by the NIH Big Data to Knowledge (BD2K) program under consortium grant U54 EB020403, by the ENIGMA World Aging Center (R56 AG058854), and by the ENIGMA Sex Differences Initiative (R01 MH116147). Additional support was provided by grants to the ENIGMA-PGC PTSD Working Group (R01 MH111671; PI: RAM), the ENIGMA-Addiction Working Group (R01 DA047119; to H.P.G. and P.J.C.), the ENIGMA Suicidal Thoughts and Behavior Working Group (R01 MH117601; to N.J. and L.S.), the ENIGMA Epilepsy Working Group (R01 NS107739; to C.R.M.), a genotyping grant from the Australian NHMRC (APP1103623 and APP1158127; to SEM), a German federal grant to the ENIGMA Task-Related fMRI Group (ER724/4-1 and WA1539/11-1; to H.W. and I.M.V.), a Kavli Foundation Neuroscience without Borders seed grant (to N.J. and P.M.T.), an NIH instrumentation grant (S10 OD023696 to P.K.), and K01 HD091283 (to S. L.L.). We thank all scientists and participants in ENIGMA who made this work possible. A full list of ENIGMA Consortium current and past members can be found here http://enigma.ini.usc.edu/ongoing/members/.

FundersFunder number
ENIGMA Sex Differences Initiative
ENIGMA World Aging Center
Kavli Foundation Neuroscience
National Institutes of HealthS10 OD023696, K01 HD091283
National Institute of Mental HealthR01 MH111671, R01 MH117601, U01MH108148, R01 MH116147
National Institute on Drug AbuseR01 DA047119
National Institute on AgingR56 AG058854, R01 AG059874
National Institute of Neurological Disorders and StrokeR01 NS107739
National Institute of Biomedical Imaging and BioengineeringU54 EB020403
National Health and Medical Research CouncilAPP1103623, APP1158127, WA1539/11-1, ER724/4-1
Deutsche Forschungsgemeinschaft


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