Age-related differences in cerebellar gene expression in autism spectrum disorder development

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that typically manifests in early infancy. Previous gene expression studies using cerebral cortex tissues from individuals with ASD have identified several differences relative to neurotypical controls. However, transcriptome studies of the cerebellum in ASD are limited, primarily due to the lack of significant differential gene expression (DGE), and the specific genes involved remain unclear. In this study, we examined gene expression differences in cerebellar tissues using RNA sequencing between individuals with ASD and neurotypical controls, stratified by age. We also investigated alternative splicing events by analysing mRNA isoform expression patterns in both age groups. The study included participants aged 4–16 years (seven ASD vs. seven controls) and participants aged 19–46 years (seven ASD vs. seven controls). Our results reveal significant differences in both mRNA expression and mRNA isoforms between ASD and control cerebellar tissues in each age group, after correction for multiple comparisons. Genes associated with ASD differed between the two age groups, and changes in isoform expression also varied with age. Although gene expression in the cerebellum has not been a primary focus of ASD research, our study demonstrated that significant differences can be observed when participants are stratified by age. This study is the first to suggest that the cerebellum is an important target for gene expression studies in ASD. Our findings further indicate that distinct genes are involved at different developmental stages of ASD, highlighting the importance of age stratification in future transcriptome studies.