HCAR3 May Mediate Autism Symptoms: Evidence From RNA-Sequencing of Peripheral Blood Mononuclear Cells

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which there is currently no effective treatment, and no reliable diagnostic biomarkers are available for ASD.

The present study was designed to compare the gene expression profiles in children with ASD and typically developing children and validate differentially expressed genes (DEGs) to assist in the search for the pathophysiological markers of ASD.

The results demonstrated the identification of 35 common DEGs with down-regulated expression and 21 with up-regulated expression. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses demonstrated that these DEGs were predominantly involved in signaling and immunity pathways. Our findings revealed that hydroxycarboxylic acid receptor 3 (HCAR3) and tumor necrosis factor ligand superfamily member 15 (TNFSF15) were associated with ASD-related symbols. Following validation by external and internal cohorts, HCAR3 may be identified as a risk gene for ASD.

Collectively, our findings indicate that some signaling-related and immune-related genes are expressed abnormally in children with ASD, and suggest that HCAR3 plays a critical role in the ASD phenotype. These findings may offer promising avenues for developing effective diagnostic biomarkers for ASD.