Network modules linking expression and methylation in prefrontal cortex of schizophrenia.
Dongdong LinJiayu ChenKuaikuai DuanNora Perrone-BizzozeroJing SuiVince CalhounJingyu LiuPublished in: Epigenetics (2020)
Tremendous work has demonstrated the critical roles of genetics, epigenetics as well as their interplay in brain transcriptional regulations in the pathology of schizophrenia (SZ). There is great success currently in the dissection of the genetic components underlying risk-conferring transcriptomic networks. However, the study of regulating effect of epigenetics in the etiopathogenesis of SZ still faces many challenges. In this work, we investigated DNA methylation and gene expression from the dorsolateral prefrontal cortex (DLPFC) region of schizophrenia patients and healthy controls using weighted correlation network approach. We identified and replicated two expression and two methylation modules significantly associated with SZ. Among them, one pair of expression and methylation modules were significantly overlapped in the module genes which were significantly enriched in astrocyte-associated functional pathways, and specifically expressed in astrocytes. Another two linked expression-methylation module pairs were involved ageing process with module genes mostly related to oligodendrocyte development and myelination, and specifically expressed in oligodendrocytes. Further examination of underlying quantitative trait loci (QTLs) showed significant enrichment in genetic risk of most psychiatric disorders for expression QTLs but not for methylation QTLs. These results support the coherence between methylation and gene expression at the network level, and suggest a combinatorial effect of genetics and epigenetics in regulating gene expression networks specific to glia cells in relation to SZ and ageing process.
Keyphrases
- genome wide
- dna methylation
- gene expression
- prefrontal cortex
- poor prognosis
- bipolar disorder
- copy number
- binding protein
- end stage renal disease
- network analysis
- high resolution
- long non coding rna
- magnetic resonance
- chronic kidney disease
- working memory
- mass spectrometry
- induced apoptosis
- signaling pathway
- transcription factor
- multiple sclerosis
- prognostic factors
- cell death
- brain injury
- peritoneal dialysis
- atomic force microscopy
- single molecule
- subarachnoid hemorrhage
- high speed