The ENIGMA Center for Worldwide Medicine, Imaging and Genomics is an unprecedented global effort bringing together 287 scientists and all their vast biomedical datasets, to work on 9 major human brain diseases: schizophrenia, bipolar disorder, major depression, ADHD, OCD, autism, 22q deletion syndrome, HIV/AIDS and addictions. ENIGMA integrates images, genomes, connectomes and biomarkers on an unprecedented scale, with new kinds of computation for integration, clustering, and learning from complex biodata types. ENIGMA, founded in 2009, performed the largest brain imaging studies in history (N>26,000 subjects;Stein +207 authors, Nature Genetics, 2012) screening genomes and images at 125 institutions in 20 countries. Responding to the BD2K RFA, ENIGMA'S Working Groups target key programmatic goals of BD2K funders across the NIH, including NIMH, NIBIB, NICHD, NIA, NINDS, NIDA, NIAAA, NHGRI and FIC. ENIGMA creates novel computational algorithms and a new model for Consortium Science to revolutionize the way Big Data is handled, shared and optimized. We unleash the power of sparse machine learning, and high dimensional combinatorics, to cluster and inter-relate genomes, connectomes, and multimodal brain images to discover diagnostic and prognostic markers. The sheer computational power and unprecedented collaboration advances distributed computation on Big Data leveraging US and non-US infrastructure, talents and data. Our projects will better identify factors that resist and promote brain disease, that help diagnosis and prognosis, and identify new mechanisms and drug targets. Our Data Science Research Cores create new algorithms to handle Big Data from (1) Imaging Genomics, (2) Connectomics, and (3) Machine Learning &Clinical Prediction. Led by world leaders in the field who developed major software packages (e.g., Jieping Ye/SLEP), we prioritize trillions of computations for gene-image clustering, distributed multi-task machine learning, and new approaches to screen brain connections based on the Partition Problem in mathematics. Our ENIGMA Training Program offers a world class Summer School coordinated with other BD2K Centers, worldwide scientific exchanges. Challenge-based Workshops and hackathons to stimulate innovation, and Web Portals to disseminate tools and engage scientists in Big Data science.

Public Health Relevance

The ENIGMA Center for Worldwide Medicine, Imaging and Genomics is an unprecedented global effort uniting 287 scientists from 125 institutions and all their vast biomedical data, to work on 9 major human brain diseases: schizophrenia, bipolar disorder, major depression, ADHD, OCD, autism, 22q deletion syndrome, HIV/AIDS and addictions. ENIGMA integrates images from multiple modalities, genomes, connectomes and biomarkers on an unimaginable scale, with new computations to integrate, cluster, and learn from complex biodata types.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BST-N (52))
Program Officer
Pai, Vinay Manjunath
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Southern California
Schools of Medicine
Los Angeles
United States
Zip Code
Hibar, Derrek P; Cheung, Joshua W; Medland, Sarah E et al. (2018) Significant concordance of genetic variation that increases both the risk for obsessive-compulsive disorder and the volumes of the nucleus accumbens and putamen. Br J Psychiatry 213:430-436
Kurth, Florian; Thompson, Paul M; Luders, Eileen (2018) Investigating the differential contributions of sex and brain size to gray matter asymmetry. Cortex 99:235-242
Adhikari, Bhim M; Jahanshad, Neda; Shukla, Dinesh et al. (2018) Comparison of heritability estimates on resting state fMRI connectivity phenotypes using the ENIGMA analysis pipeline. Hum Brain Mapp 39:4893-4902
Velthorst, Eva; Froudist-Walsh, Sean; Stahl, Eli et al. (2018) Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis. Transl Psychiatry 8:204
Carass, Aaron; Cuzzocreo, Jennifer L; Han, Shuo et al. (2018) Comparing fully automated state-of-the-art cerebellum parcellation from magnetic resonance images. Neuroimage 183:150-172
van Erp, Theo G M; Walton, Esther; Hibar, Derrek P et al. (2018) Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium. Biol Psychiatry 84:644-654
Ruggeri, Barbara; Macare, Christine; Stopponi, Serena et al. (2018) Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents. J Child Psychol Psychiatry 59:650-658
Couvy-Duchesne, Baptiste; Strike, Lachlan T; de Zubicaray, Greig I et al. (2018) Lingual Gyrus Surface Area Is Associated with Anxiety-Depression Severity in Young Adults: A Genetic Clustering Approach. eNeuro 5:
Wang, Qi; Guo, Lei; Thompson, Paul M et al. (2018) The Added Value of Diffusion-Weighted MRI-Derived Structural Connectome in Evaluating Mild Cognitive Impairment: A Multi-Cohort Validation1. J Alzheimers Dis 64:149-169
King, Joseph A; Frank, Guido K W; Thompson, Paul M et al. (2018) Structural Neuroimaging of Anorexia Nervosa: Future Directions in the Quest for Mechanisms Underlying Dynamic Alterations. Biol Psychiatry 83:224-234

Showing the most recent 10 out of 310 publications