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- Title
Structural models of genome-wide covariance identify multiple common dimensions in autism.
- Authors
de Hoyos, Lucía; Barendse, Maria T.; Schlag, Fenja; van Donkelaar, Marjolein M. J.; Verhoef, Ellen; Shapland, Chin Yang; Klassmann, Alexander; Buitelaar, Jan; Verhulst, Brad; Fisher, Simon E.; Rai, Dheeraj; St Pourcain, Beate
- Abstract
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. Studying individuals with autism only, this study investigated the genomic architecture of autism-related phenotypes using a multivariate modelling framework. This work identified distinct genomic factors linked to language performance, behaviour and developmental motor delay.
- Subjects
STRUCTURAL models; AUTISM spectrum disorders; AUTISM; DEVELOPMENTAL delay; STRUCTURAL equation modeling; PHENOTYPES; GENOMES
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-46128-8