Genetic correlates of phenotypic heterogeneity in autism
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Authors
Warrier, Varun
Zhang, Xinhe
Reed, Patrick
Havdahl, Alexandra
Moore, Tyler
Cliquet, Freddy
Leblond, Claire
Rolland, Thomas
Rosengren, Anders
Rowitch, David
Hurles, Matthew
Geschwind, Daniel
Borglum, Anders
Robinson, Elise
Grove, Jakob
Martin, Hilary
Bourgeron, Thomas
Journal Title
Nature Genetics
ISSN
1061-4036
Publisher
Nature Research
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Warrier, V., Zhang, X., Reed, P., Havdahl, A., Moore, T., Cliquet, F., Leblond, C., et al. (2022). Genetic correlates of phenotypic heterogeneity in autism. Nature Genetics https://doi.org/10.17863/CAM.84198
Abstract
The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (nmax = 12,893) based on core and associated features of autism, co-occurring developmental disabilities, and sex. We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shapes cognition, behavior, and co-occurring conditions in autism.
Sponsorship
Wellcome Trust (214322/Z/18/Z)
Identifiers
This record's DOI: https://doi.org/10.17863/CAM.84198
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336780
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