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

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 schizop...

The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data

Brain imaging and behavior, 2014

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA’s first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

ENIGMA and the Individual: Predicting Factors that Affect the Brain in 35 Countries Worldwide

NeuroImage, 2015

In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu)-a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date-of schizophrenia and major depression-ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others 1 , ENIGMA's genomic screensnow numbering over 30,000 MRI scans-have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variantsand genetic variants in general-may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures-from tens of thousands of people-that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.

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