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Journal article
Polygenic and developmental profiles of autism differ by age at diagnosis
Nature , Vol.646, pp.1146-1155
2025
PMID: 41034588
Abstract
Although autism has historically been conceptualized as a condition that emerges in early childhood1,2, many autistic people are diagnosed later in life3,4,5. It is unknown whether earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Using longitudinal data from four independent birth cohorts, we demonstrate that two different socioemotional and behavioural trajectories are associated with age at diagnosis. In independent cohorts of autistic individuals, common genetic variants account for approximately 11% of the variance in age at autism diagnosis, similar to the contribution of individual sociodemographic and clinical factors, which typically explain less than 15% of this variance. We further demonstrate that the polygenic architecture of autism can be broken down into two modestly genetically correlated (rg = 0.38, s.e. = 0.07) autism polygenic factors. One of these factors is associated with earlier autism diagnosis and lower social and communication abilities in early childhood, but is only moderately genetically correlated with attention deficit–hyperactivity disorder (ADHD) and mental-health conditions. Conversely, the second factor is associated with later autism diagnosis and increased socioemotional and behavioural difficulties in adolescence, and has moderate to high positive genetic correlations with ADHD and mental-health conditions. These findings indicate that earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Our findings have important implications for how we conceptualize autism and provide a model to explain some of the diversity found in autism.
Details
- Title
- Polygenic and developmental profiles of autism differ by age at diagnosis
- Authors
- Xinhe Zhang (Corresponding Author) - University of CambridgeJakob Grove - Aarhus UniversityYuanjun Gu - University of CambridgeCornelia K Buus - Aarhus UniversityLea K Nielsen - Aarhus UniversitySharon A S Neufeld - University of CambridgeMahmoud Koko - Wellcome Sanger InstituteDaniel S Malawsky - Wellcome Sanger InstituteEmma M Wade - Wellcome Genome CampusEllen Verhoef - Max Planck Institute for PsycholinguisticsAnna Gui - University of Rome Tor VergataLaura Hegemann - Norwegian Institute of Public HealthAPEX Consortium (Research Group)iPSYCH Autism Consortium (Research Group)PGC-PTSD Consortium (Research Group)Daniel H Geschwind - University of California, Los AngelesNaomi R Wray - The University of QueenslandAlexandra Havdahl - University of OsloAngelica Ronald - University of SurreyBeate St Pourcain - Radboud University NijmegenElise B Robinson - Broad InstituteThomas Bourgeron - Université Paris CitéSimon Baron-Cohen - University of CambridgeAnders D Børglum - Aarhus UniversityHilary C Martin - Wellcome Sanger InstituteVarun Warrier (Corresponding Author) - University of CambridgeRoss Young (Consortium Member) - University of the Sunshine Coast, Queensland, Office of the Deputy Vice-Chancellor (Research and Innovation)
- Publication details
- Nature , Vol.646, pp.1146-1155
- Publisher
- Nature Publishing Group
- Date published
- 2025
- DOI
- 10.1038/s41586-025-09542-6
- ISSN
- 1476-4687; 0028-0836
- PMID
- 41034588
- Copyright note
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Data Availability
- See article for data availability.
- Grant note
- This research was supported by funding from the Simons Foundation for Autism Research Initiative, the Wellcome Trust (214322\Z\18\Z and 226392/Z/22/Z), Horizon-Europe R2D2-MH (grant agreement 101057385) and UKRI (10063472).
- Organisation Unit
- Office of the Deputy Vice-Chancellor (Research and Innovation)
- Language
- English
- Record Identifier
- 991185244302621
- Output Type
- Journal article
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