| Title: |
Parsing Autism Heterogeneity: Transcriptomic Subgrouping of Imaging-Derived Phenotypes in Autism |
| Authors: |
Leyhausen, Johanna; Gurr, Caroline; Berg, Lisa, M; Seelemeyer, Hanna; Hermila, Bassem; Schäfer, Tim; Chiocchetti, Andreas, G; Pretzsch, Charlotte, M; Loth, Eva; Oakley, Bethany; Buitelaar, Jan, K; Beckmann, Christian, F; Charman, Tony; Bourgeron, Thomas; Barthome, Eli; Banaschewski, Tobias; Jones, Emily, Jh; Ahmad, Jumana; Ambrosino, Sara; Auyeung, Bonnie; Baron-Cohen, Simon; Baumeister, Sarah; Bölte, Sven; Bours, Carsten; Brammer, Michael; Brandeis, Daniel; Brogna, Claudia; de Bruijn, Yvette; Chakrabarti, Bhismadev; Cornelissen, Ineke; Crawley, Daisy; Dell’acqua, Flavio; Dumas, Guillaume; Durston, Sarah; Ecker, Christine; Faulkner, Jessica; Frouin, Vincent; Garcés, Pilar; Goyard, David; Ham, Lindsay; Hayward, Hannah; Hipp, Joerg; Holt, Rosemary; Johnson, Mark, H; Jones, Emily, J H; Kundu, Prantik; Lai, Meng-Chuan; D’ardhuy, Xavier, Liogier; Lombardo, Michael, V; Lythgoe, David, J; Mandl, René; Marquand, Andre; Mason, Luke; Mennes, Maarten; Meyer-Lindenberg, Andreas; Moessnang, Carolin; Bast, Nico; Murphy, Declan, G M; O’dwyer, Laurence; Oldehinkel, Marianne; Oranje, Bob; Pandina, Gahan; Persico, Antonio, M; Ruggeri, Barbara; Ruigrok, Amber; Sabet, Jessica; Sacco, Roberto; San José Cáceres, Antonia; Simonoff, Emily; Spooren, Will; Tillmann, Julian; Toro, Roberto; Tost, Heike; Waldman, Jack; Williams, Steve, C R; Wooldridge, Caroline; Zwiers, Marcel, P; Murphy, Declan |
| Contributors: |
Goethe University Frankfurt = Goethe-Universität Frankfurt am Main; King‘s College London; Radboud University Medical Center Nijmegen (RadboudUMC); Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)); Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Universität Heidelberg Heidelberg = Heidelberg University; University of London London; University of Greenwich; Universiteit Utrecht / Utrecht University Utrecht; The University of Edinburgh; University of Cambridge Cambridge, UK (CAM); Karolinska Institutet = Karolinska Institute Stockholm; Stockholm Health Care Services (SLSO); Curtin University; Donders Institute for Brain, Cognition and Behaviour; Radboud University Nijmegen; Institute of Psychiatry, Psychology & Neuroscience, King's College London; Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome (UCBM); University of Reading (UOR); Sackler Institute of Translational Neurodevelopment London; Université du Québec à Montréal = University of Québec in Montréal (UQAM); Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Germany; Universitätsklinikum Frankfurt; Service NEUROSPIN (NEUROSPIN); Université Paris-Saclay-Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA); Roche Pharma Research and Early Development Basel (pRED); F. Hoffmann-La Roche Basel; Département de Chimie Moléculaire - Ingéniérie et Intéractions BioMoléculaires (DCM - I2BM); Département de Chimie Moléculaire (DCM); Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA); Neuroanatomie Appliquée et Théorique / Applied and Theoretical Neuroanatomy (NAAT); Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115300 for the project EU-AUIMS and No 777394 for the project AIMS-2- TRIALS. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The primary contact for the EU-AIMS LEAP Group is Declan G. Murphy (Email: pa-dmurphy@kcl.ac.uk). CE gratefully acknowledges support from the German Research Foundation (DFG) (Project Nr. 551579379), the Rolf M. Schwiete Stiftung (Project Nr. 2024-022), and the DYNAMIC center funded by the LOEWE program of the Hessian Ministry of Science and Arts (Grant Number: LOEWE1/16/519/03/09.001(0009)/98). Moreover, this work was supported by the DFG-funded Transregio Aggression (TRR 379) under Project Nr. 512007073. DGM also acknowledges support from the NIHR Maudsley Biomedical Research Centre. Furthermore, this work has received funding from Horizon Europe grant agreement no. 101057385 and from UK Research and Innovation (UKRI) under the UK government’s Horizon Europe funding guarantee grant no.10039383 (R2D2-MH).; We gratefully acknowledge the contributions of the EU-AIMS LEAP Group: Jumana Ahmad, Sara Ambrosino, Bonnie Auyeung, Tobias Banaschewski, Simon Baron-Cohen, Sarah Baumeister, Christian F. Beckmann, Sven Bölte, Thomas Bourgeron, Carsten Bours, Michael Brammer, Daniel Brandeis, Claudia Brogna, Yvette de Bruijn, Jan K. Buitelaar, Bhismadev Chakrabarti, Tony Charman, Ineke Cornelissen, Daisy Crawley, Flavio Dell’Acqua, Guillaume Dumas, Sarah Durston, Christine Ecker, Jessica Faulkner, Vincent Frouin, Pilar Garcés, David Goyard, Lindsay Ham, Hannah Hayward, Joerg Hipp, Rosemary Holt, Mark H. Johnson, Emily J.H. Jones, Prantik Kundu, Meng-Chuan Lai, Xavier Liogier D’ardhuy, Michael V. Lombardo, Eva Loth, David J. Lythgoe, René Mandl, Andre Marquand, Luke Mason, Maarten Mennes, Andreas Meyer-Lindenberg, Carolin Moessnang, Nico Bast, Declan G.M. Murphy, Bethany Oakley, Laurence O’Dwyer, Marianne Oldehinkel, Bob Oranje, Gahan Pandina, Antonio M. Persico, Barbara Ruggeri, Amber Ruigrok, Jessica Sabet, Roberto Sacco, Antonia San José Cáceres, Emily Simonoff, Will Spooren, Julian Tillmann, Roberto Toro, Heike Tost, Jack Waldman, Steve C.R. Williams, Caroline Wooldridge, and Marcel P. Zwiers.; European Project: 115300,IMI-JU-03-2010,IMI-JU-03-2010,EU-AIMS(2012); European Project: 777394,H2020-JTI-IMI2-2016-10-two-stage,H2020-JTI-IMI2-2016-10-two-stage,AIMS-2-TRIALS(2018); European Project: 101057385,HORIZON-HLTH-2021-STAYHLTH-01,HORIZON-HLTH-2021-STAYHLTH-01,R2D2-MH(2022) |
| Source: |
EISSN: 2451-9022 ; Biological Psychiatry: Cognitive Neuroscience and Neuroimaging ; https://pasteur.hal.science/pasteur-05228339 ; Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2026, 11 (1), pp.80-90. ⟨10.1016/j.bpsc.2025.07.001⟩ |
| Publisher Information: |
CCSD; Elsevier |
| Publication Year: |
2026 |
| Subject Terms: |
brain structure; Stratification; Imaging-Transcriptomics; neuroimaging; structural MRI; [SCCO.NEUR]Cognitive science/Neuroscience |
| Description: |
International audience ; Background: Neurodevelopmental conditions, such as autism, are highly heterogeneous both at the mechanistic and phenotypic level. Parsing heterogeneity is therefore vital for uncovering underlying processes that could inform the development of targeted, personalized support. The study aimed to parse heterogeneity in autism by identifying subgroups that converge at both phenotypic and molecular levels.Methods: An imaging-transcriptomics approach was used to link neuroanatomical imaging-derived phenotypes in autism to whole-brain gene expression signatures provided by the Allen Human Brain Atlas. Neuroimaging and clinical data of N=359 autistic participants aged 6-30 years were provided by the EU-AIMS Longitudinal European Autism Project. Individuals were stratified using data-driven clustering techniques based on the correlation between brain phenotypes and transcriptomic profiles. The resulting subgroups were characterized on the clinical, neuroanatomical, and molecular level.Results: We identified three subgroups of autistic individuals based on the correlation between imaging-derived phenotypes and transcriptomic profiles which showed different clinical phenotypes. The individuals with the strongest transcriptomic associations to imaging-derived phenotypes showed the lowest level of symptom severity. The genesets most characteristic for each subgroup were significantly enriched for genes previously implicated in autism etiology, including processes like synaptic transmission and neuronal communication, and mapped onto different gene ontology categories.Conclusion: Autistic individuals can be sub-grouped based on the transcriptomic signatures associated with their neuroanatomical fingerprints, revealing subgroups that show differences in clinical measures. The study presents an analytical framework for linking neurodevelopmental and clinical diversity in autism to underlying molecular mechanisms, thus highlighting the need for personalized support strategies. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/40651720; info:eu-repo/grantAgreement//115300/EU/European Autism Interventions - A Multicentre Study for Developing New Medications/EU-AIMS; info:eu-repo/grantAgreement//777394/EU/Autism Innovative Medicine Studies – 2 – Trials/AIMS-2-TRIALS; info:eu-repo/grantAgreement//101057385/EU/Risk and Resilience in Developmental Diversity and Mental Health/R2D2-MH; PUBMED: 40651720 |
| DOI: |
10.1016/j.bpsc.2025.07.001 |
| Availability: |
https://pasteur.hal.science/pasteur-05228339; https://pasteur.hal.science/pasteur-05228339v1/document; https://pasteur.hal.science/pasteur-05228339v1/file/1-s2.0-S2451902225002046-main.pdf; https://doi.org/10.1016/j.bpsc.2025.07.001 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.255F90FD |
| Database: |
BASE |