Identification of the Shared Gene Signatures between Autism Spectrum Disorder and Epilepsy via Bioinformatic Analysis

To identify gene signatures that are shared by autism spectrum disorder (ASD) and epilepsy (EP) and explore the potential molecular mechanism of the two diseases using WGCNA analysis. Additionally, to verify the effects of the shared molecular mechanism on ADHD, which is another neurological comorbidity.

We screened the crosstalk genes between ASD and EP based on WGCNA and differential expression analysis from GEO and DisGeNET database and analyzed the function of the genes' enrichment by GO and KEGG analyses. Then, with combination of multiple datasets and multiple bioinformatic analysis methods, the shared gene signatures were identified. Moreover, we explored whether the shared gene signature had influence on the other neurological disorder like ADHD by analyzing the difference of the relative genes' expression based on bioinformatic analysis and molecular experiment.

By comprehensive bioinformatic analysis for multiple datasets, we found that abnormal immune response and abnormal lipid metabolic pathway played important roles in coincidence of ASD and EP. Base on the results of WGCNA, we got the hub genes in ASD and EP. In attention deficit and hyperactivity disorder (ADHD) animal model, we also found a significant difference of gene expression related to sulfatide metabolism, indicating that the abnormal sphingolipid metabolism was common in multiple neurological disorders.

This study reveals shared gene signatures between ASD and EP and identifies abnormal sphingolipid metabolism as an important participant in the development of ASD, EP, and ADHD.