Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes
Date
2018Author

Pramparo, Tiziano
Gazestani, Vahid
Warrier, Varun

Carter Barnes, Cynthia
Lopez, Linda
Lewis, Nathan E.
Eyler, Lisa
Pierce, Karen
Courchesne, Eric
ISSN
1546-1726Source
Nature NeuroscienceVolume
21Issue
12Pages
1680-1688Google Scholar check
Metadata
Show full item recordAbstract
Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD.