POS0415 BLOOD-DERIVED DNA METHYLATION EPI-SIGNATURES ASSOCIATED WITH ANKYLOSING SPONDYLITIS

Abstract

Background:Most (~90%) of the ankylosing spondylitis (AS) susceptibility loci are undefined and located in non-coding regions. Epigenetic changes may alter the expression of genes involved in AS and explain part of the missing heritability. 1Objectives:To identify novel DNA methylation sites significant for AS and comprehensively understand the underlying pathological mechanism.Methods:Genome-wide DNA methylation of blood samples from 30 AS patients and 15 health controls was measured on the Infinium® MethylationEPIC BeadChip microarray. Methylome data were analyzed with ChAMP package in R.Results:The epigenome-wide association analysis identified 4,794 differentially methylated positions (DMPs) (FDR <0.05 and delta β >0.05), including 3,294 (68.7%) hypermethylated and 1,500 (31.3%) hypomethylated positions in AS patients (Figure 1A). The identified DMPs allowed clear distinction of most AS cases from controls in the PCA (Figure 1B) and unsupervised hierarchical clustering (Figure 1C). KEGG pathway analysis of AS associated DMPs enriched in T cell receptor signaling pathway, Th1 and Th2 cell differentiation. Besides, a total of 1,048 differentially variable positions (DVPs) were identified, the majority of which (974, 92.9%) were hypervariable in AS, while only 74 DVPs were hypovariable. The increased DNA methylation variability in disease were in line with the previous observation in other diseases, indicating the intrinsic heterogeneity in AS patients, which might be influenced by diverse factors, such as disease activity and treatment.Figure 1.Conclusion:Peripheral blood mononuclear cells from AS patients display aberrant DNA methylome and increased DNA methylation variability. The results enhanced our understanding of the important role of DNA methylation in pathology of AS and offered the possibility of identifying new targets for intervention.