Blood RNA Sequencing Indicates Upregulated and and Downregulated and Expression in Children with Autism Spectrum Disorder.

Mutations in over 100 genes are implicated in autism spectrum disorder (ASD). DNA SNPs, CNVs, and epigenomic modifications also contribute to ASD. Transcriptomics analysis of blood samples may offer clues for pathways dysregulated in ASD. To expand and validate published findings of RNA-sequencing (RNA-seq) studies, we performed RNA-seq of whole blood samples from an Israeli discovery cohort of eight children with ASD compared with nine age- and sex-matched neurotypical children. This revealed 10 genes with differential expression. Using quantitative real-time PCR, we compared RNAs from whole blood samples of 73 Israeli and American children with ASD and 26 matched neurotypical children for the 10 dysregulated genes detected by RNA-seq. This revealed higher expression levels of the pro-inflammatory transcripts and and lower expression levels of the anti-inflammatory transcripts and in the ASD compared to neurotypical children. was recently reported as upregulated in blood samples of Japanese adults with ASD. Our findings support an involvement of these genes in ASD phenotypes, independent of age and ethnicity. Upregulation of and downregulation of and were reported to reduce cancer risk. Implications of the dysregulated genes for pro-inflammatory phenotypes, immunity, and cancer risk in ASD are discussed.