Network modules linking expression and methylation in prefrontal cortex of schizophrenia

• Type of Material: Article
• Authors: Dongdong Lin, Georgia State University; Jiayu Chen, Georgia State University; Kuaikuai Duan, School of Electrical and Computer Engineering; Nora Perrone-Bizzozero, The University of New Mexico; Jing Sui, Georgia State University; Vince Calhoun, Emory University; Jingyu Liu, Georgia State University
• Language: English
• Date: 2021-01-01
• Publisher: Informa UK Limited
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1080/15592294.2020.1827718
• Title of Journal or Parent Work: Epigenetics
• Volume: 16
• Issue: 8
• Start Page: 876
• End Page: 893
• Grant/Funding Information: This study was funded by the National Institutes of Health, grant number: P20GM103472, and R01EB005846, and National Science Foundation, grant number: 1539067.
• Keywords: DNA methylation; schizophrenia; ageing; brain post-mortem; Dorsolateral Prefrontal Cortex; Prefrontal Cortex; gene expression; Schizophrenia; Humans; Epigenesis, Genetic; DNA Methylation
• Research Categories: Engineering, Electronics and Electrical; Psychology, General

Abstract

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.