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Methylomic alteration in peripheral blood lymphocytes of prodromal stage and first-episode Chinese Han schizophrenia patients

By Yi Liu, Bing Lang, Robert C Smith, Guodong Wang, Jijun Wang, Yong Liu, Hua Jin, Hailong Lyu, John M. Davis, Alessandro R Guidotti, Jingping Zhao, Renrong Wu

Posted 09 Feb 2021
bioRxiv DOI: 10.1101/2021.02.07.430160

Background: Although epigenetic dysregulation has long been proposed to promote the onset of schizophrenia, the landscape of the methylomic changes across the whole genome is yet established. Methods: Using Infinium Human Methylation 850 BeadChip Array and MethylTarget sequencing method, we investigated the genome-wide methylation profiles and further validated methylation profiles of target genes in peripheral blood lymphocytes between individuals with psychosis risk syndrome (PRS), patients with first-episode schizophrenia (FES) and healthy controls (HC) in Chinese Han population. Results: We detected 372 sites between psychosis risk syndrome (PRS) and healthy controls (HC), which increased to 460 sites in first-episode schizophrenia (FES) with 207 sites shared. Both PRS and FES featured profound hypomethylation within gene body. Gene ontology and network annotation merged on loci enriched in disease associated signaling pathways (MAPK(Mitogen Activated Protein Kinases), Glutamatergic, GABAergic etc.). Conclusions: Our study implicated characteristic hypomethylation in both the discovery and validation cohorts in SYNGAP1, one of the frequently studied genes in neurodevelopmental disorders. This is the first methylome-wide association study between PRS and FES in Chinese Han population. Our findings provide potential biomarkers that can be used for future development of disease therapy and management.

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