Blood RNA Sequencing Confirms Upregulated BATF2 and FCGR1A Expression in Children with Autism Spectrum Disorder

Abstract Mutations in over 100 genes are implicated in autism spectrum disorder (ASD). DNA mutations 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 a discovery cohort of eight children with ASD compared with nine age- and sex-matched neurotypical children. This revealed 10 genes with differential expression. Using real-time PCR, we compared whole blood samples from 35 children with ASD and 21 matched neurotypical children for the 10 dysregulated genes detected by RNA-seq. This revealed higher expression levels of the proinflammatory transcripts BATF2 and FCGR1A, and lower expression levels of the anti-inflammatory transcripts ISG15 and MT2A in the ASD compared to the control group. BATF2 and FCGR1A were recently reported as upregulated in blood samples of Japanese adults with ASD. Coupled with that publication, our findings support involvement of these genes in ASD phenotypes, independent of age and ethnicity. Upregulation of BATF2 and FCGR1A and downregulation of ISG15 and MT2A were reported to reduce cancer risk. Implications of the dysregulated genes for pro-inflammatory phenotypes, immunity, and cancer risk in ASD are discussed.