Michelle Dawson posts

Post published on Bluesky on 3 Aug 2024 11:50

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DOI work Fetched Post crossref

Xinhe Zhang, Jakob Grove, Yuanjun Gu, Cornelia K. Buus, Lea K. Nielsen, Sharon A.S. Neufeld, Mahmoud Koko, Daniel S Malawsky, et al. (2024). Polygenic and developmental profiles of autism differ by age at diagnosis. openRxiv.

Publication date
2 Aug 2024
Identifier
10.1101/2024.07.31.24311279
Authors
Xinhe Zhang, Jakob Grove, Yuanjun Gu, Cornelia K. Buus, Lea K. Nielsen, Sharon A.S. Neufeld, Mahmoud Koko, Daniel S Malawsky, Emma M Wade, Ellen Verhoef, Anna Gui, Laura Hegemann, APEX consortium, iPSYCH Autism Consortium, PGC-PTSD Consortium, Daniel H. Geschwind, Naomi R. Wray, Alexandra Havdahl, Angelica Ronald, Beate St Pourcain, Elise B. Robinson, Thomas Bourgeron, Simon Baron-Cohen, Anders D. Børglum, Hilary C. Martin, Varun Warrier
Reference type
preprint
Publisher
openRxiv
Metadata source
crossref

Abstract

Abstract Although autism has been historically conceptualised as a condition that emerges in early childhood, many autistic people are diagnosed later in life. 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, comparable 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 decomposed into two modestly genetically correlated (r g = 0.38, SE = 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 modestly genetically correlated with ADHD and mental health conditions. Conversely, the second factor is associated with later autism diagnosis, increased socioemotional and behavioural difficulties in adolescence, and has moderate to high positive genetic correlations with Attention-Deficit/Hyperactivity Disorder 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 conceptualise autism and provide one model to explain some of the diversity within autism.

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