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Record W4414690425 · doi:10.1038/s41586-025-09542-6

Polygenic and developmental profiles of autism differ by age at diagnosis

2025· article· en· W4414690425 on OpenAlexaff
Jakob Grove, Yuanjun Gu, Cornelia K. Buus, Lea K. Nielsen, Sharon Neufeld, Mahmoud Koko, Daniel Malawsky, Emma E. Wade, Ellen Verhoef, Anna Gui, Carrie Allison, Alex Tsompanidis, Deep Adhya, Rosemary Holt, Omar Al-Rubaie, Ramin Ali Marandi Ghoddousi, Alexander Heazell, Jonathan Mill, Alice Franklin, Rosie Bamford, Matthew E. Hurles, Mahmoud Mousa, David H. Rowitch, Kathy K. Niakan, Graham J. Burton, Tereza Cindrová‐Davies, Deepak P. Srivastava, Lucia Dutan-Polit, Adam Pavlinek, Laura Sichlinger, Roland Nagy, Madeline A. Lancaster, José M. González, Tal Biron-Shental, Lidia V. Gabis, Dorothea L. Floris, Richard A. I. Bethlehem, Michael Lombardo, Marcin A. Radecki, Meng‐Chuan Lai, Yeshaya David M. Greenberg, Elizabeth Weir, Florina Uzefovsky, Yumnah T. Khan, Juan Pablo Del Río, Jonas Bybjerg‐Grauholm, David M. Hougaard, Preben Bo Mortensen, Merete Nordentoft, Thomas Werge, Caroline M. Nievergelt, Adam X. Maihofer, Elizabeth G. Atkinson, Chia-Yen Chen, Karmel W. Choi, Jonathan R. I. Coleman, Nikolaos P. Daskalakis, Laramie E. Duncan, Renato Polimanti, Cindy Aaronson, Ananda B. Amstadter, Søren Bo Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley‐Koch, S. Bryn Austin, Esmina Avdibegović, Dragan Babić, Silviu‐Alin Bacanu, Dewleen G. Baker, Anthony Batzler, Jean C. Beckham, Síntia Belangero, Corina Benjet, Carisa Bergner, Linda M. Bierer, Joanna M. Biernacka, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth Bolger, Amber Brandolino, Gerome Breen, Rodrigo A. Bressan, Richard A. Bryant, Angela C. Bustamante, Marie Bækvad-Hansen, Sigrid Børte, Leah Cahn, Joseph R. Calabrese, José Miguel Caldas‐de‐Almeida, Chris Chatzinakos, Sheraz Cheema, Sean Clouston, Lucía Colodro‐Conde, Brandon J. Coombes, Carlos Cruz-Fuentes, Anders M. Dale, Shareefa Dalvie, Lea K. Davis, Jürgen Deckert, Douglas L. Delahanty, Michelle F. Dennis, Frank Désarnaud, Christopher P. DiPietro, Seth G. Disner, Anna R. Docherty, Katharina Domschke, Grete Dyb, Alma Džubur Kulenović, Howard J. Edenberg, Alexandra Evans, Chiara Fabbri, Negar Fani, Lindsay A. Farrer, Adriana Feder, Norah C. Feeny, Janine D. Flory, David Forbes, Carol E. Franz, Sandro Galea, Melanie E. Garrett, Bizu Gelaye, Joel Gelernter, Charles F. Gillespie, Slavina B. Goleva, Scott D. Gordon, Afërdita Goçi, Lana Ruvolo Grasser, Camila Guindalini, Magali Haas, Saskia P. Hagenaars, Michael A. Hauser, Andrew C. Heath, Sian Hemmings, Victor Hesselbrock, Ian B. Hickie, Kelleigh Hogan, David M. Hougaard, Hailiang Huang, Laura M. Huckins, Kristian Hveem, Miro Jakovljević, Arash Javanbakht, Gregory D. Jenkins, Jessica Johnson, Ian D. Jones, Tanja Jovanović, Karen‐Inge Karstoft, Milissa L. Kaufman, Ronald C. Kessler, Nathan A. Kimbrel, Anthony P. King, Nastassja Koen, Roman Kotov, Henry R. Kranzler, Kristi Krebs, William S. Kremen, Pei Fen Kuan, Bruce R. Lawford, Lauren A. M. Lebois, Kelli Lehto, Daniel F. Levey, Israel Liberzon, Sarah D. Linnstaedt, Mark W. Logue, Adriana Lori, Yi Lu, Benjamin J. Luft, Michelle K. Lupton, Jurjen J. Luykx, Iouri Makotkine, Jessica L. Maples‐Keller, Shelby Marchese, Charles R. Marmar, Nicholas G. Martin, Gabriela Ariadna Martínez-Levy, Kerrie McAloney, Alexander C. McFarlane, Katie A. McLaughlin, Samuel A. McLean, Sarah E. Medland, Divya Mehta, Jacquelyn L. Meyers, Vasiliki Michopoulos, Elizabeth A. Mikita, William Milberg, Mark W. Miller, Rajendra A. Morey, C. Phillip Morris, Mary S. Mufford, Elliot C. Nelson, Sonya B. Norman, Nicole R Nugent, Meaghan O’Donnell, Holly K. Orcutt, Pedro Mário Pan, Matthew S. Panizzon, Gita A. Pathak, Edward Peters, Alan L. Peterson, Matthew Peverill, Robert H. Pietrzak, Melissa A. Polusny, Bernice Porjesz, Abigail Powers, Xuejun Qin, Andrew Ratanatharathorn, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy‐Byrne, Kenneth J. Ruggiero, Ariane L. Rung, Heiko Runz, Bart P. F. Rutten, Stacey Saenz de Viteri, Giovanni Abrahão Salum, Laura Sampson, Sixto E. Sánchez, Marcos Santoro, Carina Seah, Soraya Seedat, Julia S. Seng, Andrey A. Shabalin, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Scott R. Sponheim, Dan J. Stein, Synne Øien Stensland, Jennifer S. Stevens, Jennifer A. Sumner, Martin H. Teicher, Wesley K. Thompson, Arun Tiwari, Edward Trapido, Monica Uddin, Robert J. Ursano, Unnur Valdimarsdóttir, Miranda Van Hooff, Eric Vermetten, Christiaan H. Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Monika A. Waszczuk, Heike Weber, Frank R. Wendt, Michelle A. Williams, Douglas E. Williamson, Bendik S Winsvold, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Yan Xia, Xiong Ying, Rachel Yehuda, Keith A. Young, Ross McD. Young, Clement C. Zai, Gwyneth Zai, Mark Zervas, Hongyu Zhao, Lori A. Zoellner, John‐Anker Zwart, Terri A. deRoon‐Cassini, Sanne J.H. van Rooij, Leigh L. van den Heuvel, Murray B. Stein, Kerry J. Ressler, Karestan C. Koenen, Daniel H. Geschwind, Naomi R. Wray, Alexandra Havdahl, Angelica Ronald, Beaté St Pourcain, Elise Robinson, Thomas Bourgeron, Simon Baron‐Cohen, Anders D. Børglum, Hilary C. Martin, Varun Warrier

Bibliographic record

VenueNature · 2025
Typearticle
Languageen
FieldNeuroscience
TopicAutism Spectrum Disorder Research
Canadian institutionsHospital for Sick ChildrenPublic Health OntarioUniversity of TorontoCentre for Addiction and Mental Health
FundersNational Institute of Mental HealthWellcome Trust
KeywordsAutismSocioemotional selectivity theoryAutistic traitsDevelopmental disorderGenetic architecturePolygenic risk scoreAutism spectrum disorderHeritability of autism

Abstract

fetched live from OpenAlex

Abstract Although autism has historically been conceptualized as a condition that emerges in early childhood 1,2 , many autistic people are diagnosed later in life 3–5 . 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 ( r g = 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0020.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.286
Teacher spread0.274 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations26
Published2025
Admission routes1
Has abstractyes

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