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. 2022 Dec 16:2022:9883537.
doi: 10.1155/2022/9883537. eCollection 2022.

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

Yuexia Xu  1   2 , Yifeng Wang  3 , Baomei He  4 , Yuhui Yao  1   2 , Qianqian Cai  5 , Lihui Wu  1   2
Affiliations

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

Yuexia Xu et al. Comput Math Methods Med. .

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1
Figure 1
The flow diagram.
Figure 2
Figure 2
Weighted gene coexpression network analysis (WGCNA) of GSE42133. (a) Scale independence and mean connectivity. (b) The scale-free topology when β = 7. (c) The cluster dendrogram of coexpression genes in ASD. (d) Network heat map of all genes.
Figure 3
Figure 3
Weighted gene coexpression network analysis (WGCNA) of GSE143272. (a) Scale independence and mean connectivity. (b) The scale-free topology when β = 9. (c) The cluster dendrogram of coexpression genes in EP. (d) Network heat map of all genes.
Figure 4
Figure 4
Identifying significant modules of ASD and EP. (a) Module–trait relationships in ASD. Each cell contains the corresponding correlation and P value. (b) Module–trait relationships in EP. (c) Crosstalk genes between ASD and EP.
Figure 5
Figure 5
The enrichment analysis of 166 crosstalk genes. (a) Gene Ontology (GO). (b) Kyoto Encyclopedia of Genes and Genomes (KEGG).
Figure 6
Figure 6
The biological process analysis of the crosstalk genes.
Figure 7
Figure 7
The functions regulated by genes related ASD and EP from DisGeNET Database. (a) The biological process of gene enrichment related to ASD. (b) KEGG analysis of genes related to ASD. (c) The biological process of gene enrichment related to EP. (d) KEGG analysis of genes related to EP.
Figure 8
Figure 8
(a) Volcano map of ASD differentially expressed genes. (b) Volcano map of EP differentially expressed genes.
Figure 9
Figure 9
The functions regulated by crosstalk genes of ASD and EP. (a) GO analysis of the crosstalk genes. (b) KEGG analysis of the crosstalk genes. (c) Venn diagram of differentially expressed genes of ASD and EP.
Figure 10
Figure 10
Fold change expression of the objective genes in SHRs and WKYs based on GEO database.
Figure 11
Figure 11
Expression of the objective genes in whole brain of three-week-old and six-week-old model rats of ADHD.
Figure 12
Figure 12
Expression of the objective genes in specific brain regions detected by QPCR and PCR. (a) Expression of the objective genes in PFC of model rats of ADHD. (b) Expression of the objective genes in Hip of model rats of ADHD.
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References

    1. Elsabbagh M., Divan G., Koh Y. J., et al. Global prevalence of autism and other pervasive developmental disorders. Autism Research . 2012;5(3):160–179. doi: 10.1002/aur.239. - DOI - PMC - PubMed
    1. Strasser L., Downes M., Kung J., Cross J. H., De Haan M. Prevalence and risk factors for autism spectrum disorder in epilepsy: a systematic review and meta-analysis. Developmental Medicine and Child Neurology . 2018;60(1):19–29. doi: 10.1111/dmcn.13598. - DOI - PubMed
    1. Tuchman R., Rapin I. Epilepsy in autism. Lancet Neurology . 2002;1(6):352–358. doi: 10.1016/S1474-4422(02)00160-6. - DOI - PubMed
    1. Iossifov I., O’Roak B. J., Sanders S. J., et al. The contribution of _de novo_ coding mutations to autism spectrum disorder. Nature . 2014;515(7526):216–221. doi: 10.1038/nature13908. - DOI - PMC - PubMed
    1. Myers C. T., Mefford H. C. Advancing epilepsy genetics in the genomic era. Genome Medicine . 2015;7(1):p. 91. doi: 10.1186/s13073-015-0214-7. - DOI - PMC - PubMed

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