Mega‐analysis methods in ENIGMA: The experience of the generalized anxiety disorder working group

Abstract

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

ENIGMA‐Sleep: Challenges, opportunities, and the road map

“…cortical thickness of brain areas) individual data are shared and pooled across the sites, leading to a potentially higher power and greater flexibility (e.g. by enabling us to apply machine learning methods that require individual data), at the cost of lower number of participating sites, and more computational/storage requirements at the pooling site (Zugman et al, 2020).…”

Altered Task-Evoked Corticolimbic Responsivity in Generalized Anxiety Disorder

“…Of course, practical issues such as limited resources prevent individual research groups and labs from performing large-scale data collection and analysis. As such, perhaps a multisite collaborative effort such as the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium [5] may be a useful means to counter the drawbacks of underpowered individual studies, as well as gain a clearer picture of abnormal brain functional responsivity patterns in GAD. For such efforts to achieve greater heights, the development of specific tasks and experimental paradigms that are tailored to probe GAD psychopathology would be useful.…”

“…As with many other psychiatric disorders, researchers have sought to discover and develop potential brain-based biomarkers for GAD via structural and functional neuroimaging methods [5]. Magnetic resonance imaging (MRI), in particular, offers a non-invasive means to measure diverse properties of the human brain, including regional volume, functional responsivity to psychological tasks, functional architecture at rest, and connectivity.…”

ENIGMA + COINSTAC: Improving Findability, Accessibility, Interoperability, and Re-usability

“…Through concerted efforts to bring in researchers from around the world, ENIGMA has grown into a massive collaborative effort organized around over 50 working groups focused on clinical studies, methodological approach development for a range of imaging modalities (MRI, diffusion imaging, resting-state fMRI and EEG), and genetic as well as epigenetic analyses. The methods have expanded to include data sharing and centralized aggregation for some analyses, allowing for a "mega-analysis" rather than meta-analyses, e.g., (Boedhoe et al, 2018;Ching et al, 2020a;Hoogman et al, 2020;Zugman et al, 2020), though the data aggregation approach limits participation by sites who are not allowed to share individual data points due to local regulations and ethical concerns. In short, the consortium has supported coordinated immensely powerful analyses that are entirely distributed, or entirely centralized, as well as combinations of each approach.…”