A Pathway Analysis Based on Genome-Wide DNA Methylation of Chinese Patients with Graves' Orbitopathy. (13th January 2019)

• Record Type: Journal Article
• Authors: Xin, Zhong; Hua, Lin; Yang, Yi-Lin; Shi, Ting-Ting; Liu, Wei; Tuo, Xiu; Li, Yu; Cao, Xi; Yang, Fang-Yuan
• Other Names: Bogdanos Dimitrios P. Academic Editor.
• Is Part Of: BioMed research international. Volume 2019(2019)
• Publication Date: 2019-01-13
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2019/9565794
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : Background . The pathogenesis Graves' Orbitopathy (GO) is not yet fully understood. Here, we conducted a pathway analysis based on genome-wide DNA methylation data of Chinese GO patients to explore GO-related pathways and potential feature genes. Methods . Six GO patients and 6 age-matched control individuals were recruited, and a genome-scale screen of DNA methylation was measured using their peripheral blood sample. After extracting the differentially methylated regions (DMRs), we classified DMRs into three clusters with respect to median absolute deviation (MAD) for GO and control group, respectively. Then the extract tests were performed to identify significant pathways by comparing the counts of genes in each cluster between GO and control group in a pathway. For each significant pathway, we calculated the Methylation-based Inference of Regulatory Activity (MIRA) score to infer the regulatory activity of genes involved in the pathway. Furthermore, we took the significant pathways as the subsets and applied Random forests (RF) method to extract GO-related feature genes. Results . We identified four potential significant pathways associated with the occurrence and development of GO disease. There were Toxoplasmosis, Axon guidance, Focal adhesion, and Proteoglycans in cancer (p<0.001 or p=0.007). The identified genes involved in the significant pathways, such as LDLR (p=0.019), CDK5 (p=0.036), and PIK3CB (p=0.020), were found to be correlated with GO phenotype. Conclusion . Our study suggested pathway analyses can help understand the potential relationships between the DNA methylation level of some certain genes and their regulation in Chinese GO patients.