Funding

Funding for ENIGMA comes from a variety of sources. Core funding for the ENIGMA Center for Worldwide Medicine Imaging and Genomics was provided as part of the 2014 NIH Big Data to Knowledge (BD2K) Initiative under U54EB020403 (PI: Paul Thompson) to support big data analytics, management and distribution of programs.

Support for data collection and site-level analysis is provided by individual group studies
from around the world including Africa, Asia, Australia, Europe, North America, and South America. These include:
NHMRC, DCRC, BMBF, Swedish Research Council, German Ministry of Cultural Affairs, Social Ministry of the Federal State of Mecklenburg–West Pomerania, NGFN, Siemens, ISCIII, SENY Fundació, NOW, BBMRI-NL, CBF, Hersenstichting Nederland, Alzheimer’s Australia Dementia Research Foundation, Autism Speaks, NIMH, NIBIB, NICHD, NINDS, NIA

 
 

Core Grants:

ENIGMA-OCD: WORLDWIDE COLLABORATION TO UNDERSTAND HOW OCD SHAPES THE BRAIN, IOCDF Innovator Award
PI: Odile A. van den Heuvel for ENIGMA-OCD
Granted: June 2021

GENETIC INFLUENCES ON INFANT BRAIN DEVELOPMENT: UNDERSTANDING THE DEVELOPMENTAL ORIGINS OF MENTAL ILLNESS, NIMH R01
PI: Rebecca Knickmeyer for ENIGMA-ORIGINs
Granted: May 2021
The primary goal of the current application is to determine how genetic factors influence the development of brain structure and function in infancy and early childhood. Several major disorders emerge during this period, including autism and ADHD, and altered brain development at this early stage may increase risk for later-onset disorders such as schizophrenia. This project will provide new insights into the developmental origins of psychi- atric disease and inspire an exciting new line of research focused on preventing psychiatric conditions through very early intervention in at-risk individuals. Read more.

REDEFINE TRANS-NEUROPSYCHIATRIC DISORDER BRAIN PATTERNS THROUGH BIG-DATA AND MACHINE LEARNING, NIA RF1
PI: Peter Kochunov, Paul M. Thompson
Granted: April 2021
The Connectomes Related to Human Disease/Human Connectome Project (CRHD) and Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) are two large scale NIH-funded initiatives exploring disorder-related patterns in the human brain. The two projects are complementary: CRHD focuses on in-depth, high-resolution multimodal phenotyping of the brain connectome in modest samples, whereas ENIGMA’s analyses harness the statistical power of large and inclusive, worldwide samples. We propose combining the strengths of CRHD and ENIGMA to test novel biomarkers based on replicable and consistent illness deficit patterns provided by Big Data studies. We posit that major brain illnesses do not impact an isolated region or brain circuit but rather lead to deficit patterns across multiple brain regions and circuits that are shared or unique to an illness; such deficit patterns are highly replicable and linked to severity, duration and treatment resistance. We will develop and evaluate a multivariate vulnerability model based on (1) the degree of similarity between an individual’s brain patterns and expected disorder patterns defined as a linear combination of deficits – conceptually similar to polygenic risk scores – and (2) a vulnerability metric computed using machine learning. We will test the specificity and sensitivity of these models against the single most discriminative neuroimaging traits in six diagnostic categories shared by CRHD and ENIGMA: schizophrenia-spectrum disorders (SSD) and psychosis, major depressive disorder (MDD), bipolar disorders (BP), epilepsy (EP), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). We will use multivariate analyses to compare sensitivity and specificity of the regional vulnerability index (RVI) and machine learning vulnerability (MVI) in separating patients and controls in the CHRD samples, mapping unique and shared deficit patterns across six diagnostic categories. We will link vulnerability metrics to cognitive outcomes and diagnosis using mediation analyses. Finally, we will enrich vulnerability models with CHRD’s connectomics based phenotypes including cortical myelination to advance white matter integrity measurements for future large-scale ENIGMA studies. Read more and see details.

ENIGMA-ANXIETY: BEHAVIORAL INHIBITION, Rubicon grant from the Dutch Research Council (NWO)
PI: Janna Marie Bas-Hoogendam and Daniel Pine for ENIGMA-Anxiety
Granted: March 2021

ENIGMA WORLD AGING CENTER, NIA R01
PI: Paul M. Thompson for the ENIGMA-Lifespan, Epigenetics, Plasticity & Aging working groups
Granted: January 2021
To address reproducibility and power issues in aging and Alzheimer’s disease research, we launch ENIGMA’s World Aging Center, a global brain study of aging and AD across 45 countries. Leveraging our ENIGMA network (340 institutions), we launch 4 coordinated projects to empower genetic and epigenetic studies of brain aging: (1) Enigma-Lifespan- creates normative charts of brain aging metrics from MRI, diffusion imaging, and functional MRI in 20,000 people worldwide; (2) ENIGMA-Epigenetics- relates genome-wide methylation to brain aging; (3) ENIGMA-Plasticity- seeking genetic loci affecting brain atrophy rates; and (4) ENIGMA-Alzheimer’s- to identify how Alzheimer’s genetic risk and new risk scores for accelerated tissue loss, affect the brain. We will analyze worldwide imaging, epigenetic, and clinical data with harmonized methods, to create new aging “clocks” and reveal targetable risk factors and modifiers of brain aging in the genome and blood, worldwide.Read more.
Visit: https://ewac.ini.usc.edu/

IDENTIFYING THE COGNITIVE, PSYCHOLOGICAL, AND NEUROIMAGING SIGNATURES OF HEAD TRAUMA IN FEMALE SURVIVORS OF INTIMATE PARTNER VIOLENCE – NINDS R01
PI: Carrie L. Esopenko with Frank G. Hillary, Alex P. Lin, David F. Tate for ENIGMA-Intimate Partner Violence
Granted: January 2021
Narrative Physical trauma as an outcome of intimate partner violence (IPV) impacts an estimated 10 million people in the United States each year, with up to 90% of women exposed to IPV reporting episodes of abuse with head trauma. Women exposed to IPV are at a high-risk for developing mental illness and impaired cognitive function, which seems to be compounded in those with exposure to head trauma. This proposal aims to investigate the impact exposure to head trauma in IPV has on cognitive, psychological, and neural processes. Read more.

ADVANCING SECONDARY DATA ANALYSIS: THE ENIGMA BRAIN INJURY DATA HARMONIZATION INITIATIVE – NINDS R61
PI: Frank G. Hillary with Emily L. Dennie, David F. Tate, Elisabeth A. Wilde for ENIGMA-TBI
Granted: September 2020
Traumatic brain injury (TBI) can cause widespread alteration in brain structure and function, but sample size in imaging studies is often limited, and differences in data acquisition and variables can create obstacles to data sharing. We propose to develop an open-source workflow for utilizing behavioral and MRI data that addresses these concerns and allows for harmonization across sites, supporting “big data” analyses that can identify clinically-meaningful patient subgroups in TBI, a goal that is not feasible with small datasets. Achieving the proposed Aims will make a curated and harmonized dataset available to the TBI community as well as procedures and data processing pipelines adaptable to other disorders in the clinical neurosciences. Read more.

EFFECTS OF GLOBAL BRAIN HEALTH ON SENSORIMOTOR RECOVERY AFTER STROKE, NIH R01
PI: Sook-Lei Liew for the ENIGMA-Stroke Recovery working group
Granted: April 2020
This research is relevant to public health because it will uncover new neurobiological influences on how people regain motor and sensory function after a stroke. Specifically, this study will examine the role of global brain health measures, which represent deterioration of systems across the whole brain, in stroke recovery by analyzing both: (a) a large existing database of neuroimaging and behavioral data on stroke patients and (b) new data that will be collected in the first 3 months following stroke, when the majority of stroke recovery is thought to occur. The project is relevant to the NIH’s mission because it will create important new knowledge on the relationships of global brain health to post-stroke brain injury, brain repair, and sensorimotor recovery, which can be used to identify novel therapeutic targets to improve stroke recovery. Read more.

ENIGMA GOES FUNCTIONAL – EXPLORING THE NEUROGENETIC ARCHITECTURE OF BRAIN (DYS)FUNCTION , DFG (Germany)
PI: Henrik Walter for the ENIGMA-task based fMRI working group
Granted: 2019
This project adopts the meta-analytic approach of the ENIGMA consortium to analyze a sufficiently large sample of functional imaging data to allow genome-wide association analysis with intermediate phenotypes within the RDoC framework. In this project, we will focus on three functional imaging tasks that fall within the functional RDoC domains, and are associated with psychiatric disease: 1) an emotional faces task (negative valence domain), 2) a monetary incentive delay task (positive valence domain), and 3) a working memory task (cognitive domain). All these tasks have been used widely in the imaging genetics community with only slight variations in task design or stimuli. We aim to collect samples of about ~10,000 subjects per task. This sample size is expected to have sufficient power to reliably detect genetic association.

NEURODEGENERATION IN SPINOCEREBELLAR ATAXIAS (SCAs): BIOMARKERS, MECHANISMS, AND VARIABILITY, NHMRC (Australia)
PI: Ian Harding for the ENIGMA-Ataxia working group
Granted: January 2020
Localising and quantifying molecular markers of oxidative stress and neuroinflammation, investigating their links with macroscopic neurodegeneration, and validating their utility as markers of disease status have great potential for characterising and tracking neurodegenerative diseases. This line of research is not only critically relevant to SCAs, but will also provide mechanistic insights into more common disorders that share these pathways (e.g., dementias).

ENIGMA-APOE2: A GLOBAL STUDY OF THE ALZHEIMER’S PROTECTIVE GENOTYPE, Zenith Fellows Award (Alzheimer’s Association)
PI: Paul Thompson for the ENIGMA-Plasticity, Lifespan & EEG working groups
Granted: September 2019
Our ENIGMA APOE2 Initiative will use our vibrant network to coordinate 3 studies of the APOE2 Alzheimer’s disease protective genotype. ENIGMA’s successful genomic screen of the brain’s memory system was awarded the Kent Innovation in Academia Prize for uniting researchers globally (Hibar 2017). ENIGMA’s Lifespan, EEG, and Plasticity studies will examine international data on brain function and microstructure, to understand how APOE2 exerts its protective effects, and test if they generalize worldwide.

INDIA ENIGMA INITIATIVE FOR GLOBAL AGING & MENTAL HEALTH, NIA R01
PI: Paul Thompson
Granted: September 2019
We launch the India ENIGMA Initiative for Global Aging & Mental Health – a globally coordinated study of brain aging and Alzheimer’s disease (AD). Our overall goal is to identify predictive markers in the blood, genome, and epigenome, and psychosocial/lifestyle factors that influence brain aging in India, to better understand prognosis, and to support personalized risk evaluations on each continent. We plan to identify etiological pathways to resilience using the rich biobanking strategy developed by our partners at NIMHANS in India. Read more.

ENIGMA-COINSTAC: ADVANCED WORLDWIDE TRANSDIAGNOSTIC ANALYSIS OF VALENCE SYSTEM BRAIN CIRCUITS, NIMH R01
PIs: Jessica Turner, Vince Calhoun & Theo van Erp for the ENIGMA-Schizophrenia working group
Granted: August 2019
This study is an unprecedented effort that leverages multiple worldwide working groups along with machine learning via a sophisticated decentralized analysis framework. The study findings will validate and extend the Research Domain Criteria (RDoC) matrix framework that links negative symptom domains (behavior) -via positive valence and social processing systems and their subconstructs – to brain structures/circuitry (physiology). The findings will yield novel classification approaches for negative symptom severity, may identify novel treatment targets (circuitry), and may yield classifications to stratify patients to treatment conditions. Read more.

PREDICTION OF SEIZURE LATERALIZATION AND POSTOPERATIVE OUTCOME THROUGH THE USE OF DEEP LEARNING APPLIED TO MULTI-SITE MRI/DTI DATA: AN ENIGMA-EPILEPSY STUDY, NINDS R21
MPIs: Carrie McDonald & Leonardo Bonilha for the ENIGMA-Epilepsy working group
Granted: April 2019
Epilepsy is a devastating neurological illness, affecting 65 million people worldwide. In this project, we will leverage the ENIGMA-Epilepsy infrastructure to address how advanced, non-invasive neuroimaging can be used to develop algorithms for (1) lateralizing the seizure focus and (2) predicting favorable versus unfavorable surgical outcomes. The research will be accomplished by applying novel machine learning algorithms to clinical and imaging data on an exceptionally large cohort of patients with epilepsy and healthy controls, providing unprecedented power to tackle critical diagnostic and treatment-related questions in epilepsy. Read more.

USING STATISTICAL GENETICS TO ELUCIDATE THE EFFECTS OF DISEASE ASSOCIATED GENETIC VARIANTS WITHIN THE HUMAN BRAIN, NHMRC (Australia)
PI: Sarah Medland for the ENIGMA-Genetics working group
Granted: January 2019
Genome-wide association studies (GWAS) for psychiatric disorders and neurological diseases have been highly successful and have led to the identification of new treatment targets and biomarkers for a wide range of diseases and traits. Follow up molecular analyses are underway for many of these loci and while it is typically assumed that the effects of these loci should be studied within the brain, it is unclear which brain regions should be studied. Using existing collaborations among members of the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, the proposed project seeks funds to obtain genotyping for an additional 6,000 ENIGMA participants for whom Magnetic Resonance Imaging (MRI) and DNA samples are already available and use GWAS to conduct in vivo mapping of the effects of common genetic variants on brain derived phenotypes (including volume, surface area, thickness and connectivity between regions). Leveraging the data from phenotypic case/control studies within ENIGMA we will also be able to determine whether the regions associated with disease associated variants are significantly associated with that disease at a phenotypic level and examine the causality of these effects through Mendelian randomisation. The results of these analyses will be distributed through a freely available searchable database (currently being built within ENIGMA) providing visual mapping of the effects of common genetic variants across the genome on key brain regions. This will allow researchers to query the extent to which anatomical phenotypes are associated with variants of interest.

ENIGMA-SD: UNDERSTANDING SEX DIFFERENCES IN GLOBAL MENTAL HEALTH THROUGH ENIGMA, NIMH R01
PI: Paul Thompson for the ENIGMA-MDD, BD, Schizophrenia, PTSD & Addiction/Substance Use Disorders working groups
Granted: May 2018
Many brain disorders, including depression, PTSD, and anxiety are more prevalent in women than men, but others (such as drug addiction) are more common in men. Here we build on our worldwide consortium, ENIGMA, to study sex differences in brain aging, in the trajectories of 5 major psychiatric illnesses: major depression, bipolar illness, schizophrenia, post-traumatic stress disorder (PTSD), and substance use disorders (SUDs). Our project offers the unprecedented power of a global study across 35 countries, to pick up sex-specific shifts in the age of onset, severity, and trajectory of brain disease across the world. Read more.

ENIGMA-ADDICTION: POOLING OF EXISTING DATASETS TO IDENTIFY BRAIN AND GENETIC CORRELATES OF ADDICTION, NIDA R01
PIs: Hugh Garavan, Patricia Conrod for the ENIGMA-Addictions/Substance Use Disorders working group
Granted: September 2018
The ENIGMA-Addiction consortium (http://enigma.ini.usc.edu/) was established to understand the genomic and neurobiological correlates of substance abuse by combining existing genomic and brain imaging datasets. Its goal is to maximize the yield from existing datasets through very large data pooling efforts thereby providing statistical power for rigorous and reproducible analyses. This application seeks to develop this consortium beyond its proof-of-concept stage by identifying genetic and environmental influences on brain markers of dependence using an expanded number of brain measures and to make the data available through the creation of a data analysis portal. Read more.

A GLOBAL ALLIANCE TO UNLOCK BRAIN MECHANISMS INFLUENCING SUICIDAL BEHAVIORS THROUGH THE ENIGMA CONSORTIUM, NIMH R01
PIs: Neda Jahanshad & Lianne Schmaal for the ENIGMA-Suicidal Thoughts & Behaviors working group
Granted: August 2018
Despite many efforts to prevent suicide, suicides and suicide attempts continue to increase in the US. Better prevention strategies are urgently needed; yet, mechanisms that confer increased risk for suicidal ideation and attempt remain largely unknown. The proposed study, with its large sample size and strong methodology, will allow us to investigate, systematically, mechanisms underlying suicidal behaviors, and the results from this study can inform the development of novel preventions. Read more.

TRAUMA AND GENOMICS MODULATE BRAIN STRUCTURE ACROSS COMMON PSYCHIATRIC DISORDERS, NIMH R01
PI: Rajendra Morey for the ENIGMA-PGC-PTSD working group
Granted: September 2017
Exposure to trauma and abuse during childhood, a critical neurodevelopmental period, is a major risk factor for developing psychiatric conditions in adulthood. Our goal is to search for genes in adults who were exposed to psychological trauma (abuse, neglect) as children and develop psychiatric illness in adulthood in order to identify genetic variants that produce alterations in brain structure evident with MRI. Our long-term goal is to identify genetic modulators of brain structure that might inform early prediction and treatment for a range of psychiatric disorders where childhood trauma is a major risk factor. Read more.
 
 

Past Grants (completed):

ENIGMA CENTER FOR WORLDWIDE MEDICINE, IMAGING & GENOMICS, NIBIB/cross-NIH U54
PI: Paul Thompson for the ENIGMA-Schizophrenia, BD, MDD, ADHD, OCD, ASD, 22q deletion syndrome, HIV/AIDS & Addiction/Substance Use Disorders working groups
Granted: September 2014
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. Read more.

NEURODATA WITHOUT BORDERS: ENIGMA, Kavli Foundation, for their Neurodata without Borders Pilot series
PIs: Neda Jahanshad & Paul Thompson for ENIGMA’s informatics core
Granted: January 2017

BIG DATA NEUROIMAGING TO PREDICT MOTOR BEHAVIOR AFTER STROKE, NICHD K01
PI: Sook-Lei Liew for the ENIGMA-Stroke Recovery working group
Granted: April 2017
The overall goal of this project is to provide personalized, precise rehabilitation medicine to individuals after stroke by developing accurate predictive models that help us detect who will recover and best respond to different types of post-stroke treatments. Using a novel meta-analytic approach, this project will harmonize datasets of brain imaging and behavioral information across sites worldwide in order to develop a large dataset with thousands of participants. Advanced statistical and machine learning techniques will then be applied to this dataset in order to detect robust neural and behavioral biomarkers that can be used to predict stroke recovery and to personalize treatments across diverse populations. Read more.

A WORLDWIDE EFFORT TO RELIABLY MAP ALTERED BRAIN CIRCUITRY IN PARKINSON’S DISEASE PATIENTS AND THOSE AT GENETIC RISK, Michael J. Fox Foundation
PI: Neda Jahanshad for the ENIGMA-Parkinson’s Disease working group
Granted: November 2017

ENIGMA WORLD AGING CENTER, NIA R56
PI: Paul Thompson for the ENIGMA-Lifespan, Epigenetics, Epilepsy & Plasticity working groups
Granted: September 2018
To address reproducibility and power issues in aging research, we launch ENIGMA’s World Aging Center, a global brain aging study across 35 countries. Leveraging our ENIGMA network (340 institutions), we launch 4 coordinated projects to empower genetic, epigenetic, and environmental studies of brain aging: (1) ENIGMA-Lifespan- creates normative charts of brain aging metrics from MRI, diffusion imaging, and functional MRI in 10,000+ people worldwide; (2) ENIGMA-Epigenetics- relates genome-wide methylation to brain aging; (3) ENIGMA-Plasticity- seeking genetic loci affecting brain atrophy rates; and (4) ENIGMA-Parkinson’s- to identify surrogate markers of PD for treatment trials. We will analyze worldwide imaging, epigenetic, and clinical data with harmonized methods, to create new aging “clocks” and reveal targetable risk factors and modifiers of brain aging in the genome, blood, and environment. Read more.
For more information, visit https://ewac.ini.usc.edu/

 
 

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