Structural models of genome-wide covariance identify multiple common dimensions in autism.

Autor: de Hoyos L; Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands., Barendse MT; Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.; Department of Social Dentistry and Behavioural Sciences, Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands., Schlag F; Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands., van Donkelaar MMJ; Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands., Verhoef E; Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands., Shapland CY; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Population Health Sciences, University of Bristol, Bristol, UK., Klassmann A; Institute for Genetics, University of Cologne, Cologne, Germany., Buitelaar J; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.; Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.; Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands., Verhulst B; Texas A&M University, College Station, TX, USA., Fisher SE; Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands., Rai D; Population Health Sciences, University of Bristol, Bristol, UK.; Avon and Wiltshire Partnership NHS Mental Health Trust, Bristol, UK.; NIHR Biomedical Research Centre, University of Bristol, Bristol, UK., St Pourcain B; Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands. Beate.StPourcain@mpi.nl.; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. Beate.StPourcain@mpi.nl.; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands. Beate.StPourcain@mpi.nl.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 27; Vol. 15 (1), pp. 1770. Date of Electronic Publication: 2024 Feb 27.
DOI: 10.1038/s41467-024-46128-8
Abstrakt: Common genetic variation has been associated with multiple phenotypic features in Autism Spectrum Disorder (ASD). However, our knowledge of shared genetic factor structures contributing to this highly heterogeneous phenotypic spectrum is limited. Here, we developed and implemented a structural equation modelling framework to directly model genomic covariance across core and non-core ASD phenotypes, studying autistic individuals of European descent with a case-only design. We identified three independent genetic factors most strongly linked to language performance, behaviour and developmental motor delay, respectively, studying an autism community sample (N = 5331). The three-factorial structure was largely confirmed in independent ASD-simplex families (N = 1946), although we uncovered, in addition, simplex-specific genetic overlap between behaviour and language phenotypes. Multivariate models across cohorts revealed novel associations, including links between language and early mastering of self-feeding. Thus, the common genetic architecture in ASD is multi-dimensional with overarching genetic factors contributing, in combination with ascertainment-specific patterns, to phenotypic heterogeneity.
(© 2024. The Author(s).)
Databáze: MEDLINE
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