In a groundbreaking effort to unravel the complex genetic and environmental factors contributing to eating disorders, the Eating Disorders Genetics Initiative 2 (EDGI2) has launched an ambitious international study protocol set to transform our understanding of conditions such as anorexia nervosa, bulimia nervosa, binge-eating disorder, and avoidant/restrictive food intake disorder (ARFID). Building upon the foundation of previous genetic research in psychiatry, EDGI2 aims to bridge significant gaps by focusing on a more diverse population and including underexplored disorders like ARFID within its scope.
This global initiative envisions the recruitment of 20,000 new participants distributed across continents, encompassing the United States, Mexico, Australia, Aotearoa New Zealand, Sweden, and Denmark. The study targets an extensive sample size composed predominantly of individuals diagnosed with eating disorders (approximately 18,700 cases) paired with 1,300 control subjects. Such scale and diversity underscore the innovative essence of EDGI2, setting a new benchmark in genetic epidemiology by incorporating broad ancestral backgrounds and severe, longstanding cases.
EDGI2 employs a comprehensive methodology combining deep phenotyping with advanced genotyping techniques. Participants in most countries provide saliva samples and complete a detailed questionnaire battery curated explicitly for this initiative. Sweden and Denmark utilize national registries and historical biobanked specimens, respectively, demonstrating the project’s adaptability to varied national infrastructures. This harmonization of multiple data sources enables robust genome-wide association studies (GWAS), which will be conducted both internally and through collaborative meta-analyses with the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED).
One of the defining features of EDGI2 is its commitment to exploring the genetic architecture of eating disorders beyond traditional diagnostic classifications. By integrating case–control and case-case GWAS approaches, the study aims to dissect genomic variations unique to specific disorders and those shared across the spectrum. This nuanced analysis could illuminate the overlapping and divergent biological pathways underlying these complex psychiatric conditions, providing insights that might guide precision medicine approaches in the future.
Additionally, the study places significant emphasis on evaluating genetic correlations between eating disorders and other psychiatric and metabolic traits. This approach acknowledges the pleiotropic nature of many genetic risk factors and their potential influence on a broad range of phenotypes. Calculated polygenic risk scores (PRS) derived from the data will serve as quantitative measures of inherited susceptibility, offering avenues for patient stratification and personalized intervention strategies.
The integration of functional biology represents another pivotal aspect of EDGI2’s design. By linking identified risk loci to clinical outcomes, researchers hope to translate genetic findings into meaningful clinical contexts, thereby addressing one of the major challenges in psychiatric genetics. Understanding how genetic variants modulate symptom severity, treatment response, or comorbidity patterns will be vital for transforming genetic insights into improved clinical care.
EDGI2 emerges at a critical juncture in psychiatric research, where eating disorders have historically been underrepresented. The initiative’s expansive recruitment strategy and inclusive approach seek to redress this imbalance, recognizing the heterogeneity and complexity inherent to these conditions. The inclusion of ARFID, a relatively newer diagnostic entity characterized by restrictive eating without a body image disturbance, further broadens the investigative lens, promising novel discoveries that could reshape diagnostic frameworks.
This protocol also showcases the power of international collaboration in psychiatric genomics. By combining datasets from multiple countries and leveraging existing biobank resources, EDGI2 maximizes statistical power and the generalizability of its findings. Such large-scale consortia are essential for dissecting subtle genetic effects that would remain undetectable in smaller cohorts.
Importantly, the study is registered as a clinical trial (ClinicalTrials.gov NCT06594913), underscoring its commitment to transparency and rigorous standards. This formal registration facilitates tracking of study progress, data sharing, and adherence to ethical guidelines, thereby enhancing trust in the scientific community and among participants.
Looking ahead, the expected outcomes from EDGI2 could have profound implications for how eating disorders are conceptualized, diagnosed, and treated. By pinpointing genetic contributors and their interplay with environmental exposures, researchers aspire to unravel the etiological complexity that challenges effective intervention. Moreover, PRS and risk loci identified through the study have the potential to serve as biomarkers, guiding early detection and tailored therapeutic approaches.
In summary, EDGI2 represents a monumental stride forward, encapsulating the confluence of advanced genomics, psychiatry, and international collaboration. Its design accommodates diverse populations and integrates cutting-edge analytic techniques, marking a paradigm shift toward a more comprehensive understanding of eating disorders. As data collection progresses, the scientific community eagerly anticipates insights that will not only deepen biological understanding but also catalyze innovations in clinical management, ultimately benefiting millions affected worldwide.
Subject of Research: Genetics and environmental factors of eating disorders including anorexia nervosa, bulimia nervosa, binge-eating disorder, and ARFID.
Article Title: The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol
Article References:
Berthold, N., MacDermod, C.M., Thornton, L.M. et al. The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol. BMC Psychiatry 25, 532 (2025). https://doi.org/10.1186/s12888-025-06777-5
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