Novel insights into the biological underpinnings of autism in individuals from simplex families through the application of phenotypic subtyping and re-analyses of existing transcriptomic data
Open AccessAutism spectrum disorder (ASD) describes a collection of neurodevelopmental disorders that have as core symptoms social communication deficits as well as restricted interests and repetitive, stereotyped behaviors. Primary challenges to understanding and treating ASD are the genetic and phenotypic heterogeneity of cases that complicates all ‘omics analyses as well as a lack of information on relationships between genes and autistic traits. In this study, we re-analyze existing transcriptomic data from simplex families by subtyping individuals with ASD according to multivariate cluster analyses of ADI-R scores that encompass a broad range of symptoms. We also correlate multiple ASD traits with expression profiles using Weighted Gene Correlation Network Analyses (WGCNA).Our results show that subtyping greatly enhances the ability to identify different pathways and biological functions associated with ASD within each subgroup. Moreover, using WGCNA, we identify gene modules that correlate significantly with specific ASD traits, especially in the verbal-nonverbal communication domains. Network prediction analyses of the genes in these modules reveal canonical pathways as well as neurological functions and disorders relevant to the pathobiology of ASD. Finally, we compare the WGCNA-derived data on autistic traits in simplex families with analogous data from multiplex families using transcriptomic data from our previous studies.
- All rights reserved
Notice to Authors
If you are the author of this work and you have any questions about the information on this page, please use the Contact form to get in touch with us.