Table 2.
Potential DNA methylation markers in autism spectrum disorders.
| Cell/Tissue Type | Main Findings | Ref. |
|---|---|---|
| ASD | ||
| Postmortem brain tissues from ASD patients and HCs | Increased MECP2 interaction with RELN and GAD1 gene promoters triggers the reduction of Reelin and GAD67 expression in the CB and FC of patients with ASD compared to HCs. | [61] |
| Postmortem brain tissues from ASD patients and HCs | Hypomethylation and overexpression of immune-related genes (such as C1Q, C3, ITGB2, and TNF-α) were observed in the PFC of ASD compared to HCs. | [62] |
| Postmortem tissues from ASD patients and HCs | Hypomethylation of CpG sites in the promoters of immune genes leads to an upregulated immune process in the convergent subtype. | [63] |
| Frozen brain samples from ASD and HCs | A total of 58 ASD-associated DMRs were enriched for genomic regions of neuronal, GABAergic, and immune system genes. | [64] |
| Cord, blood, and brain tissues from ASD and HCs | ASD-associated meQTLs across the genome were enriched for immune-related pathways in the cord, blood, and brain tissues of children with ASD. | [65] |
| PBMCs from children with ASD and HCs | Methylation and expression levels of BDNF in blood samples from children with ASD can use as a diagnostic biomarker. | [66] |
| PB from adults with high-functioning ASD and HCs | Hypermethylation of a CpG site (cg20793532) in the PPP2R2C promoter can serve as a blood biomarker for identifying adult patients with high-functioning ASD. | [67] |
| Blood DNA from male ASD patients and HCs | Most of the 700 DMCpGs (587; 83.9%) in ASD cases showed relative hypomethylation compared to HCs. Hypomethylation and overexpression of ERMN contribute to ASD susceptibility and can be altered by both rare SNPs at the CG position and mutations. | [68] |
| WB samples from ASD-discordant MZ twins, ASD-concordant MZ twins, and a set of pairs of sporadic case-control | A total of 2,397 DAGs were associated with neurotrophin signaling pathway in ASD-discordant MZ twins. The aberrant methylation of SH2B1 was identified in the ASD-discordant, ASD-concordant MZ twins, and sporadic cases compared to controls. | [69] |
| Lymphoblastoid cells from idiopathic ASD and unaffected sex-matched siblings | DAGs were associated with synaptogenesis, semaphorin, and mTOR pathways in idiopathic ASD compared to unaffected sex-matched siblings. | [70] |
| Placenta samples stored from children later diagnosed with ASD compared to typically developing controls | A total of 400 DMRs can distinguish placentas stored from children later diagnosed with ASD relative to typically developing controls. Methylation levels of two DMRs, mapping on CYP2E1 and IRS2, can serve as a useful predictive biomarker for ASD risk in placenta samples. | [71] |
ASD: autism spectrum disorder; BDNF: brain-derived neurotrophic factor; CB: cerebellum; C1Q: complement component 1q; C3: complement component 3; CYP2E1: cytochrome P450 family 2 subfamily E member 1; DMRs: differentially methylated regions; DMCpGs: differentially methylated CpGs; DAGs: DMR-associated genes; DNMT: DNA (cytosine-5)-methyltransferase; ERMN: ermin; FC: frontal cortex; GAD1: glutamate decarboxylase 1; GAD67: glutamate decarboxylase 67; HCs: healthy controls; ITGB2: integrin subunit beta 2; IRS: insulin receptor substrate; MZ: monozygotic; meQTLs: methylation quantitative trait loci; mTOR: mechanistic target of rapamycin; PFC: prefrontal cortex; PB: peripheral blood; PBMNs: peripheral blood mononuclear cells; PPP2R2C: protein phosphatase 2 regulatory subunit b gamma; PMS: polymethylation score; RELN Reelin; SH2B1: SH2B adaptor protein 1; TNF-α: tumor necrosis factor-α; WB: whole blood.