European Autism GEnomics Registry (EAGER): protocol for a multicentre cohort study and registry

Madeleine Bloomfield; Alexandra Lautarescu; Síofra Heraty; Sarah Douglas; Pierre Violland; Roderik Plas; Anjuli Ghosh; Katrien Van den Bosch; Eliza Eaton; Michael Absoud; Roberta Battini; Ana Blázquez Hinojosa; Nadia Bolshakova; Sven Bölte; Paolo Bonanni; Jacqueline Borg; Sara Calderoni; Rosa Calvo Escalona; Miguel Castelo-Branco; Josefina Castro-Fornieles; Pilar Caro; Freddy Cliquet; Alberto Danieli; Richard Delorme; Maurizio Elia; Maja Hempel; Claire S Leblond; Nuno Madeira; Grainne McAlonan; Roberta Milone; Ciara J Molloy; Susana Mouga; Virginia Montiel; Ana Pina Rodrigues; Christian P Schaaf; Mercedes Serrano; Kristiina Tammimies; Charlotte Tye; Federico Vigevano; Guiomar Oliveira; Beatrice Mazzone; Cara O'Neill; Julie Pender; Verena Romero; Julian Tillmann; Bethany Oakley; Declan G M Murphy; Louise Gallagher; Thomas Bourgeron; Christopher Chatham; Tony Charman

doi:10.1136/bmjopen-2023-080746

European Autism GEnomics Registry (EAGER): protocol for a multicentre cohort study and registry

BMJ Open. 2024 Jun 4;14(6):e080746. doi: 10.1136/bmjopen-2023-080746.

Authors

Madeleine Bloomfield¹, Alexandra Lautarescu^{2

3}, Síofra Heraty⁴, Sarah Douglas⁵, Pierre Violland⁵, Roderik Plas⁵, Anjuli Ghosh⁵, Katrien Van den Bosch⁵, Eliza Eaton⁶, Michael Absoud^{7

8}, Roberta Battini^{9

10}, Ana Blázquez Hinojosa¹¹, Nadia Bolshakova¹², Sven Bölte^{13

14

15}, Paolo Bonanni¹⁶, Jacqueline Borg^{17

18

19}, Sara Calderoni^{9

10}, Rosa Calvo Escalona^{11

20

21

22}, Miguel Castelo-Branco^{23

24}, Josefina Castro-Fornieles^{11

20

21

22}, Pilar Caro²⁵, Freddy Cliquet²⁶, Alberto Danieli¹⁶, Richard Delorme²⁷, Maurizio Elia²⁸, Maja Hempel²⁵, Claire S Leblond²⁶, Nuno Madeira^{24

29

30}, Grainne McAlonan^{3

31}, Roberta Milone⁹, Ciara J Molloy¹², Susana Mouga²⁴, Virginia Montiel³², Ana Pina Rodrigues²⁴, Christian P Schaaf²⁵, Mercedes Serrano³², Kristiina Tammimies^{13

33}, Charlotte Tye¹, Federico Vigevano^{34

35}, Guiomar Oliveira^{24

36

37}, Beatrice Mazzone⁹, Cara O'Neill³⁸, Julie Pender³⁹, Verena Romero⁴⁰, Julian Tillmann⁴¹, Bethany Oakley³, Declan G M Murphy^{3

42

43}, Louise Gallagher^{12

44

45

46}, Thomas Bourgeron²⁶, Christopher Chatham⁴⁷, Tony Charman¹

Affiliations

¹ Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
² Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK alexandra.lautarescu@kcl.ac.uk.
³ Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology, & Neuroscience, King's College London, London, UK.
⁴ Department of Psychological Sciences, Birkbeck University of London, London, UK.
⁵ AIMS-2-TRIALS A-Reps, Cambridge University, Cambridge, UK.
⁶ Autism Research Centre, Cambridge University, Cambridge, UK.
⁷ Department of Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' Hospitals NHS Trust, London, UK.
⁸ Department of Women and Children's Health, Faculty of Life Sciences and Medicine, School of Life Course Sciences, King's College London, London, UK.
⁹ Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris, Pisa, Italy.
¹⁰ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
¹¹ Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic Universitari Barcelona, Barcelona, Spain.
¹² Department of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland.
¹³ Center of Neurodevelopmental Disorders (KIND), Department of Women's and Children's Health, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
¹⁴ Child and Adolescent Psychiatry, Stockholm Health Care Services, Stockholm, Sweden.
¹⁵ Curtin Autism Research Group, Curtin School of Allied Health, Curtin University, Perth, Western Australia, Australia.
¹⁶ Epilepsy Unit, Scientific Institute IRCCS E. Medea Conegliano, Treviso, Italy.
¹⁷ Centre for Psychiatry Research and Centre for Cognitive and Computational Neuropsychiatry (CCNP), Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm, Sweden.
¹⁸ Department of Neuropsychiatry, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹⁹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at The University of Gothenburg, Gothenburg, Sweden.
²⁰ Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
²¹ Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
²² Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
²³ Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
²⁴ Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute of Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal.
²⁵ Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany.
²⁶ Génétique Humaine et Fonctions Cognitives, UMR3571 CNRS, Institut Pasteur, Paris, France.
²⁷ Child and Adolescent Psychiatry Department, Robert Debre Hospital, APHP, Paris, France.
²⁸ Unit of Neurology and Clinical Neurophysiopathology, Oasi Research Institute-IRCCS, Troina, Italy.
²⁹ Psychiatry Department, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal.
³⁰ Institute of Psychological Medicine, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
³¹ Behavioural and Developmental Clinical Academic Group, South London and Maudsley NHS Foundation Trust, London, UK.
³² Pediatric Neurology Department, Hospital Sant Joan de Déu, Institut de Recerca Sant Joan de Deu, Barcelona, Spain.
³³ Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
³⁴ Neurological Sciences and Rehabilitation Medicine Scientific Area, Bambino Gesù Children's Hospital, Rome, Italy.
³⁵ Paediatric Neurorehabilitation Department, IRCCS San Raffaele, Rome, UK.
³⁶ University Clinic of Pediatrics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
³⁷ Child Developmental Center and Research and Clinical Training Center, Pediatric Hospital, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal.
³⁸ Cure Sanfilippo Foundation, Columbia, South Carolina, USA.
³⁹ SYNGAP Research Fund, San Diego, California, USA.
⁴⁰ Dup15q e.V, Hessen, Germany.
⁴¹ Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland.
⁴² South London and Maudsley NHS Foundation Trust, London, UK.
⁴³ Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁴⁴ SickKids Research Institute, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁴⁵ Child and Youth Division Centre for Addiction and Mental Health, CAMH, Toronto, Ontario, Canada.
⁴⁶ Department of Psychiatry, Temerty Faculty of Medicine, Univerisity of Toronto, Toronto, Ontario, Canada.
⁴⁷ F Hoffmann-La Roche Ltd, Basel, Switzerland.

Abstract

Introduction: Autism is a common neurodevelopmental condition with a complex genetic aetiology that includes contributions from monogenic and polygenic factors. Many autistic people have unmet healthcare needs that could be served by genomics-informed research and clinical trials. The primary aim of the European Autism GEnomics Registry (EAGER) is to establish a registry of participants with a diagnosis of autism or an associated rare genetic condition who have undergone whole-genome sequencing. The registry can facilitate recruitment for future clinical trials and research studies, based on genetic, clinical and phenotypic profiles, as well as participant preferences. The secondary aim of EAGER is to investigate the association between mental and physical health characteristics and participants' genetic profiles.

Methods and analysis: EAGER is a European multisite cohort study and registry and is part of the AIMS-2-TRIALS consortium. EAGER was developed with input from the AIMS-2-TRIALS Autism Representatives and representatives from the rare genetic conditions community. 1500 participants with a diagnosis of autism or an associated rare genetic condition will be recruited at 13 sites across 8 countries. Participants will be given a blood or saliva sample for whole-genome sequencing and answer a series of online questionnaires. Participants may also consent to the study to access pre-existing clinical data. Participants will be added to the EAGER registry and data will be shared externally through established AIMS-2-TRIALS mechanisms.

Ethics and dissemination: To date, EAGER has received full ethical approval for 11 out of the 13 sites in the UK (REC 23/SC/0022), Germany (S-375/2023), Portugal (CE-085/2023), Spain (HCB/2023/0038, PIC-164-22), Sweden (Dnr 2023-06737-01), Ireland (230907) and Italy (CET_62/2023, CEL-IRCCS OASI/24-01-2024/EM01, EM 2024-13/1032 EAGER). Findings will be disseminated via scientific publications and conferences but also beyond to participants and the wider community (eg, the AIMS-2-TRIALS website, stakeholder meetings, newsletters).

Keywords: genetics; mental health; registries.

MeSH terms

Autistic Disorder* / genetics
Child
Cohort Studies
Europe
Genomics*
Humans
Male
Multicenter Studies as Topic
Registries*
Research Design
Whole Genome Sequencing*