Genome-wide analysis of DNA methylation in 106 schizophrenia family trios in Han Chinese

EBioMedicine

Xi Wu¹  Cong Huai²  Xiaoying Lv³  Mo Li⁴  Hailiang Huang⁵  Lei Cai⁶  Lin He⁷  Hao Wu⁸  Shengying Qin⁸  Yana Lu⁸  Jingsong Ma⁸  Saizheng Weng⁸  Yidan Sun⁸  Yi Shi⁸  Lixing Li⁸  Ting Wang⁸  Luan Chen⁸  Chao Yang⁸  Yan Zhang⁸  Lu Shen⁸  Jie Tan⁸  Chunling Wan⁹  Na Zhang^1,10  Shaobin Tai^1,11 

[1] Broad Institute of Harvard and MIT, Cambridge, MA, USA;Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences, Shanghai 200031, PR China;Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China;Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;DCH Technologies Inc, Cambridge, MA 02142, USA;Department of General Surgery, School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China;Fuzhou Neuro-psychiatric hospital, Fujian Medical University, Fuzhou 350026, China;Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, PR China;The Second People's Hospital of Huangshan, Huangshan 245021, China;The Second People's Hospital of Lishui, Lishui 323020, China;Wuxi Mental Health Center, Nanjing Medical University, Wuxi 214151, China;

关键词: Schizophrenia;    DNA Methylation;    Trios;    Chinese;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Schizophrenia (SCZ) is a severe psychiatric disorder that affects approximately 0.75% of the global population. Both genetic and environmental factors contribute to development of SCZ. SCZ tends to run in family while both genetic and environmental factor contribute to its etiology. Much evidence suggested that alterations in DNA methylations occurred in SCZ patients. Methods: To investigate potential inheritable pattern of DNA methylation in SCZ family, we performed a genome-wide analysis of DNA methylation of peripheral blood samples from 106 Chinese SCZ family trios. Genome-wide DNA methylations were quantified by Agilent 1 × 244 k Human Methylation Microarray. Findings: In this study, we proposed a loci inheritance frequency model that allows characterization of differential methylated regions as SCZ biomarkers. Based on this model, 112 hypermethylated and 125 hypomethylated regions were identified. Additionally, 121 hypermethylated and 139 hypomethylated genes were annotated. The results of functional enrichment analysis indicated that multiple differentially methylated genes (DMGs) involved in Notch/HH/Wnt signaling, MAPK signaling, GPCR signaling, immune response signaling. Notably, a number of hypomethylated genes were significantly enriched in cerebral cortex and functionally enriched in nervous system development. Interpretation: Our findings not only validated previously discovered risk genes of SCZ but also identified novel candidate DMGs in SCZ. These results may further the understanding of altered DNA methylations in SCZ. Funding: None.

【 授权许可】

Unknown