Schizophrenia is a serious and debilitating neurodevelopmental disorder that typically occurs in early adulthood. DNA methylation, a critical epigenetic modification, contributes to alter gene expression without affecting the underlying genomic sequences; 5-methycytosine (5mC) and 5-hydroxylcytosine (5hmC) are two major forms of DNA methylation in mammals.
DMRs | Tissues | Expression | 5mC | Phenotypes | References |
---|---|---|---|---|---|
KLF9 | Human cortical grey and white matter | ↓ | ↑ | rs11142387 near the KLF9 was significantly associated with psychiatric disease and poor memory function. | [28] |
SFXN1 | Human cortical grey and white matter | ↓ | ↑ | The loss of SPRED2 leads to defective glycine and purine synthesis. | [28] |
SPRED2 | Human cortical grey and white matter | ↓ | ↑ | The loss of SPRED2 leads to a phenotype resembling recessive Noonan syndrome. | [28] |
ALS2CL | Human cortical grey and white matter | ↑ | ↓ | Mutations in ALS2CL may contribute to the development of schizophrenia. | [28] |
RELN | Human peripheral blood | ↓ | ↑ | Single-allele and biallelic mutations in RELN can lead to neurodevelopmental disorders. The dysregulation of RELN expression has been observed in patients with schizophrenia and bipolar disorder. | [29,30][29][30] |
BDNF | Human peripheral blood | ↓ | ↑ | BDNF activates the tyrosine kinase receptor B (TrkB), triggering various downstream signaling pathways. In patients with schizophrenia, there are alterations in BDNF signaling transduction. | [31] |
SLC6A3 | Isohelix swab pack | ↓ | ↑ | SLC6A3 is associated with several neurological and psychiatric disorders, including ADHD, autism, cognitive impairments, movement disorders, and schizophrenia. | [32,33][32][33] |
DTNBP1 | Human brain | ↓ | ↑ | The aberrant expression of DTNBP1B is associated with cognitive deficits in schizophrenia. | [34,35,36][34][35][36] |
GAD1 | Human | ↓ | ↑ | The GAD1-knockout mouse model exhibits impairments in spatial memory and working memory. It shows reduced locomotor activity in new environments and a decreased preference for novel stimuli. | [37] |
COMT | Human peripheral blood | ↑ | ↑ | The deletion of the COMT gene can lead to a range of complex complications, with psychiatric symptoms manifesting as schizophrenia and other mental disorders. | [38] |
DhMRs | Tissues | Expression | 5hmC | Phenotypes | References |
---|---|---|---|---|---|
GABRB2 | Human, peripheral white blood cells | ↓ | ↑ | Gabrb2-knockout mice exhibit anxiety-like and depression-like behavioral changes, as well as alterations in social behavior, learning, and memory abilities. | [85] |
GAD67 | Human, parietal cortex | ↓ | ↑ | GAD67-knockout mice exhibit emotional and auditory abnormalities, as well as anxiety-like behavior. | [87,88][87][88] |
APOBEC3A/C | Human, parietal cortex and prefrontal cortex | ↓ | ↑ | The deletion of APOBEC3A has been associated with an increased susceptibility to early-onset breast cancer. | [87] |
GADD45b | ↑ | ↑ | The knockdown of Gadd45b in the amygdala of neonatal rats leads to changes in social behavior during adolescence and a decrease in the expression of several genes associated with psychiatric disorders, including MeCP2, Reelin, and BDNF. | [89] | |
BDNF IX | ↓ | ↑ | BDNF knockout mice exhibit chronic liver disease, specifically non-alcoholic fatty liver disease (NAFLD). | [89] | |
GRIN2C | Monkey, cerebellum | ↓ | - | The knockdown of PAX6 in differentiating human limbal epithelial cells leads to a decrease in the expression of FABP5 and DSG1 proteins. | unpublished data |
PAX6 | ↑ | - | unpublished data |