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Transcriptional subtyping explains phenotypic variability in genetic subtypes of autism spectrum disorder

Published online by Cambridge University Press:  11 September 2020

Sandy Trinh*
Department of Educational Psychology, University of Washington, Seattle, WA, USA
Anne Arnett
Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA, USA Department of Psychiatry & Behavioral Medicine, Seattle Children's Hospital, Seattle, WA, USA
Evangeline Kurtz-Nelson
Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA, USA
Jennifer Beighley
Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA, USA
Marta Picoto
Department of Educational Psychology, University of Washington, Seattle, WA, USA
Raphael Bernier
Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA, USA
Author for correspondence: Sandy Trinh, MS, University of Washington, Department of Educational Psychology, Box 353600, Seattle, WA98195; E-mail:


Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by deficits in social communication and presence of restricted, repetitive behaviors, and interests. However, individuals with ASD vary significantly in their challenges and abilities in these and other developmental domains. Gene discovery in ASD has accelerated in the past decade, and genetic subtyping has yielded preliminary evidence of utility in parsing phenotypic heterogeneity through genomic subtypes. Recent advances in transcriptomics have provided additional dimensions with which to refine genetic subtyping efforts. In the current study, we investigate phenotypic differences among transcriptional subtypes defined by neurobiological spatiotemporal co-expression patterns. Of the four transcriptional subtypes examined, participants with mutations to genes typically expressed highly in all brain regions prenatally, and those with differential postnatal cerebellar expression relative to other brain regions, showed lower cognitive and adaptive skills, higher severity of social communication deficits, and later acquisition of speech and motor milestones, compared to those with mutations to genes highly expressed during the postnatal period across brain regions. These findings suggest higher-order characterization of genetic subtypes based on neurobiological expression patterns may be a promising approach to parsing phenotypic heterogeneity among those with ASD and related neurodevelopmental disorders.

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Copyright © The Author(s), 2020. Published by Cambridge University Press

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Both authors contributed equally to this work.


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