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

Heterogeneity in early language development in autism spectrum disorders (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here we identify a large-scale association between multiple coordinated blood leukocyte gene co-expression modules and multivariate functional neuroimaging (fMRI) response to speech. Gene co-expression modules associated with multivariate fMRI response to speech are different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and either poor versus good early language outcome. Associated co-expression modules are enriched in genes that are broadly expressed in the brain and many other tissues. These co-expression modules are also enriched for ASD, 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.