The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol

Abstract Background The Eating Disorders Genetics Initiative 2 (EDGI2) is designed to explore the role of genes and environment in anorexia nervosa, bulimia nervosa, binge-eating disorder, and avoidant/restrictive food intake disorder (ARFID) with a focus on broad population representation and sever...

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Main Authors: Natasha Berthold, Casey M. MacDermod, Laura M. Thornton, Richard Parker, Shantal Anid Cortés Morales, Liv Hog, Hannah L. Kennedy, Jerry Guintivano, Patrick F. Sullivan, James J. Crowley, Jessica S. Johnson, Andreas Birgegård, Bengt T. Fundín, Emma Frans, Jiayi Xu, Michaela Pettie “Ngāti Pūkenga”, Allison L. Miller, Mariana Valdez Aguilar, Sarah Barakat, Mohamed Abdulkadir, Jennifer P. White, Janne T. Larsen, Elsie Trujillo, Bertha Winterman, Ruyue Zhang, Rachel Lawson, Stephen Wonderlich, Joseph Wonderlich, Lauren M. Schaefer, Philip S. Mehler, Judy Oakes, Marina Foster, Jennifer Gaudiani, Eva Trujillo Chi Vacuán, Emilio J. Compte, Liselotte V. Petersen, Zeynep Yilmaz, Nadia Micali, Jennifer Jordan, Martin A. Kennedy, Sarah Maguire, Laura M. Huckins, Yi Lu, Lisa Dinkler, Nicholas G. Martin, Cynthia M. Bulik
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-06777-5
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author Natasha Berthold
Casey M. MacDermod
Laura M. Thornton
Richard Parker
Shantal Anid Cortés Morales
Liv Hog
Hannah L. Kennedy
Jerry Guintivano
Patrick F. Sullivan
James J. Crowley
Jessica S. Johnson
Andreas Birgegård
Bengt T. Fundín
Emma Frans
Jiayi Xu
Michaela Pettie “Ngāti Pūkenga”
Allison L. Miller
Mariana Valdez Aguilar
Sarah Barakat
Mohamed Abdulkadir
Jennifer P. White
Janne T. Larsen
Elsie Trujillo
Bertha Winterman
Ruyue Zhang
Rachel Lawson
Stephen Wonderlich
Joseph Wonderlich
Lauren M. Schaefer
Philip S. Mehler
Judy Oakes
Marina Foster
Jennifer Gaudiani
Eva Trujillo Chi Vacuán
Emilio J. Compte
Liselotte V. Petersen
Zeynep Yilmaz
Nadia Micali
Jennifer Jordan
Martin A. Kennedy
Sarah Maguire
Laura M. Huckins
Yi Lu
Lisa Dinkler
Nicholas G. Martin
Cynthia M. Bulik
author_facet Natasha Berthold
Casey M. MacDermod
Laura M. Thornton
Richard Parker
Shantal Anid Cortés Morales
Liv Hog
Hannah L. Kennedy
Jerry Guintivano
Patrick F. Sullivan
James J. Crowley
Jessica S. Johnson
Andreas Birgegård
Bengt T. Fundín
Emma Frans
Jiayi Xu
Michaela Pettie “Ngāti Pūkenga”
Allison L. Miller
Mariana Valdez Aguilar
Sarah Barakat
Mohamed Abdulkadir
Jennifer P. White
Janne T. Larsen
Elsie Trujillo
Bertha Winterman
Ruyue Zhang
Rachel Lawson
Stephen Wonderlich
Joseph Wonderlich
Lauren M. Schaefer
Philip S. Mehler
Judy Oakes
Marina Foster
Jennifer Gaudiani
Eva Trujillo Chi Vacuán
Emilio J. Compte
Liselotte V. Petersen
Zeynep Yilmaz
Nadia Micali
Jennifer Jordan
Martin A. Kennedy
Sarah Maguire
Laura M. Huckins
Yi Lu
Lisa Dinkler
Nicholas G. Martin
Cynthia M. Bulik
author_sort Natasha Berthold
collection DOAJ
description Abstract Background The Eating Disorders Genetics Initiative 2 (EDGI2) is designed to explore the role of genes and environment in anorexia nervosa, bulimia nervosa, binge-eating disorder, and avoidant/restrictive food intake disorder (ARFID) with a focus on broad population representation and severe and/or longstanding illness. Methods A total of 20,000 new participants (18,700 cases and 1,300 controls) will be ascertained from the United States (US), Mexico (MX), Australia (AU), Aotearoa New Zealand (NZ), Sweden (SE), and Denmark (DK). Comprehensive phenotyping and genotyping will be performed for participants in US, MX, AU, NZ, and SE using the EDGI2 questionnaire battery and participant saliva samples. In DK, case identification and genotyping will be through the National Patient Register and bloodspots archived near birth. Case–control and case-case genome-wide association studies will be conducted within EDGI2 and enhanced via meta-analysis with external data from the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED). Additional analyses will explore genetic correlations between eating disorders (EDs) and other psychiatric and metabolic traits, calculate polygenic risk scores (PRS), and leverage functional biology to evaluate clinical outcomes. Moreover, analyzing PRS for patient stratification and linking identified risk loci to clinically relevant phenotypes highlight the potential of EDGI2 for clinical translation. Discussion EDGI2 is a global expansion of the EDGI study to increase sample size, increase participant representation across multiple ancestral backgrounds, and to include ARFID. ED genetics research has historically lagged behind other psychiatric disorders, and EDGI2 is designed to rapidly advance the study of the genetics of the major EDs. Exploring EDs at both the diagnostic level and the symptom level will provide an unprecedented look at the genetic architecture underlying EDs. Trial registration EDGI2 is a registered clinical trial: clinicaltrials.gov NCT06594913. https://clinicaltrials.gov/study/NCT06594913 (posted September 19, 2024).
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spelling doaj-art-8eabe4ed29c7486d9da3757f4928d2a82025-08-20T03:22:12ZengBMCBMC Psychiatry1471-244X2025-05-0125111610.1186/s12888-025-06777-5The Eating Disorders Genetics Initiative 2 (EDGI2): study protocolNatasha Berthold0Casey M. MacDermod1Laura M. Thornton2Richard Parker3Shantal Anid Cortés Morales4Liv Hog5Hannah L. Kennedy6Jerry Guintivano7Patrick F. Sullivan8James J. Crowley9Jessica S. Johnson10Andreas Birgegård11Bengt T. Fundín12Emma Frans13Jiayi Xu14Michaela Pettie “Ngāti Pūkenga”15Allison L. Miller16Mariana Valdez Aguilar17Sarah Barakat18Mohamed Abdulkadir19Jennifer P. White20Janne T. Larsen21Elsie Trujillo22Bertha Winterman23Ruyue Zhang24Rachel Lawson25Stephen Wonderlich26Joseph Wonderlich27Lauren M. Schaefer28Philip S. Mehler29Judy Oakes30Marina Foster31Jennifer Gaudiani32Eva Trujillo Chi Vacuán33Emilio J. Compte34Liselotte V. Petersen35Zeynep Yilmaz36Nadia Micali37Jennifer Jordan38Martin A. Kennedy39Sarah Maguire40Laura M. Huckins41Yi Lu42Lisa Dinkler43Nicholas G. Martin44Cynthia M. Bulik45Department of Psychiatry, University of North Carolina at Chapel HillDepartment of Psychiatry, University of North Carolina at Chapel HillDepartment of Psychiatry, University of North Carolina at Chapel HillQIMR Berghofer Medical Research Institute, Royal Brisbane HospitalResearch Department, Comenzar de NuevoDepartment of Medical Epidemiology and BiostatisticsDepartment of Pathology and Biomedical Science, University of OtagoDepartment of Psychiatry, University of North Carolina at Chapel HillDepartment of Psychiatry, University of North Carolina at Chapel HillDepartment of Medical Epidemiology and BiostatisticsDepartment of Psychiatry, University of North Carolina at Chapel HillDepartment of Medical Epidemiology and BiostatisticsDepartment of Medical Epidemiology and BiostatisticsDepartment of Medical Epidemiology and BiostatisticsDivision of Molecular Psychiatry, Department of Psychiatry, Yale UniversityDepartment of Pathology and Biomedical Science, University of OtagoDepartment of Pathology and Biomedical Science, University of OtagoDepartment of Psychiatry, University of North Carolina at Chapel HillInsideout Institute for Eating Disorders, The University of SydneyDepartment of Public Health, National Centre for Register-Based Research, Aarhus UniversityDepartment of Psychiatry, University of North Carolina at Chapel HillDepartment of Public Health, National Centre for Register-Based Research, Aarhus UniversityResearch Department, Comenzar de NuevoResearch Department, Comenzar de NuevoDepartment of Medical Epidemiology and BiostatisticsSouth Island Eating Disorders Service, Health NZ Te Whatu OraCenter for Biobehavioral Research, Sanford HealthCenter for Biobehavioral Research, Sanford HealthCenter for Biobehavioral Research, Sanford HealthACUTE Center for Eating Disorders and Severe Malnutrition, Denver Health and Hospital AuthorityACUTE Center for Eating Disorders and Severe Malnutrition, Denver Health and Hospital AuthorityACUTE Center for Eating Disorders and Severe Malnutrition, Denver Health and Hospital AuthorityGaudiani ClinicResearch Department, Comenzar de NuevoResearch Department, Comenzar de NuevoDepartment of Public Health, National Centre for Register-Based Research, Aarhus UniversityDepartment of Psychiatry, University of North Carolina at Chapel HillCenter for Eating and Feeding Disorders Research, Mental Health Services of the Capital Region of DenmarkDepartment of Psychological Medicine, University of OtagoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud – Insideout Institute for Eating Disorders, The University of SydneyDivision of Molecular Psychiatry, Department of Psychiatry, Yale UniversityDepartment of Medical Epidemiology and BiostatisticsDepartment of Medical Epidemiology and BiostatisticsQIMR Berghofer Medical Research Institute, Royal Brisbane HospitalDepartment of Psychiatry, University of North Carolina at Chapel HillAbstract Background The Eating Disorders Genetics Initiative 2 (EDGI2) is designed to explore the role of genes and environment in anorexia nervosa, bulimia nervosa, binge-eating disorder, and avoidant/restrictive food intake disorder (ARFID) with a focus on broad population representation and severe and/or longstanding illness. Methods A total of 20,000 new participants (18,700 cases and 1,300 controls) will be ascertained from the United States (US), Mexico (MX), Australia (AU), Aotearoa New Zealand (NZ), Sweden (SE), and Denmark (DK). Comprehensive phenotyping and genotyping will be performed for participants in US, MX, AU, NZ, and SE using the EDGI2 questionnaire battery and participant saliva samples. In DK, case identification and genotyping will be through the National Patient Register and bloodspots archived near birth. Case–control and case-case genome-wide association studies will be conducted within EDGI2 and enhanced via meta-analysis with external data from the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED). Additional analyses will explore genetic correlations between eating disorders (EDs) and other psychiatric and metabolic traits, calculate polygenic risk scores (PRS), and leverage functional biology to evaluate clinical outcomes. Moreover, analyzing PRS for patient stratification and linking identified risk loci to clinically relevant phenotypes highlight the potential of EDGI2 for clinical translation. Discussion EDGI2 is a global expansion of the EDGI study to increase sample size, increase participant representation across multiple ancestral backgrounds, and to include ARFID. ED genetics research has historically lagged behind other psychiatric disorders, and EDGI2 is designed to rapidly advance the study of the genetics of the major EDs. Exploring EDs at both the diagnostic level and the symptom level will provide an unprecedented look at the genetic architecture underlying EDs. Trial registration EDGI2 is a registered clinical trial: clinicaltrials.gov NCT06594913. https://clinicaltrials.gov/study/NCT06594913 (posted September 19, 2024).https://doi.org/10.1186/s12888-025-06777-5Anorexia nervosaBulimia nervosaBinge-eating disorderAvoidant/restrictive food intake disorderGenome-wide associationPsychiatric genetics
spellingShingle Natasha Berthold
Casey M. MacDermod
Laura M. Thornton
Richard Parker
Shantal Anid Cortés Morales
Liv Hog
Hannah L. Kennedy
Jerry Guintivano
Patrick F. Sullivan
James J. Crowley
Jessica S. Johnson
Andreas Birgegård
Bengt T. Fundín
Emma Frans
Jiayi Xu
Michaela Pettie “Ngāti Pūkenga”
Allison L. Miller
Mariana Valdez Aguilar
Sarah Barakat
Mohamed Abdulkadir
Jennifer P. White
Janne T. Larsen
Elsie Trujillo
Bertha Winterman
Ruyue Zhang
Rachel Lawson
Stephen Wonderlich
Joseph Wonderlich
Lauren M. Schaefer
Philip S. Mehler
Judy Oakes
Marina Foster
Jennifer Gaudiani
Eva Trujillo Chi Vacuán
Emilio J. Compte
Liselotte V. Petersen
Zeynep Yilmaz
Nadia Micali
Jennifer Jordan
Martin A. Kennedy
Sarah Maguire
Laura M. Huckins
Yi Lu
Lisa Dinkler
Nicholas G. Martin
Cynthia M. Bulik
The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol
BMC Psychiatry
Anorexia nervosa
Bulimia nervosa
Binge-eating disorder
Avoidant/restrictive food intake disorder
Genome-wide association
Psychiatric genetics
title The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol
title_full The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol
title_fullStr The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol
title_full_unstemmed The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol
title_short The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol
title_sort eating disorders genetics initiative 2 edgi2 study protocol
topic Anorexia nervosa
Bulimia nervosa
Binge-eating disorder
Avoidant/restrictive food intake disorder
Genome-wide association
Psychiatric genetics
url https://doi.org/10.1186/s12888-025-06777-5
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