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• W3165194266 abstract "Abstract Gene-environment interactions play a pivotal role in the pathogenesis of Inflammatory Bowel Disease (IBD). Using the IBD Character inception cohort (295 controls, 154 CD, 161 UC, 28 IBD-U) we confirm the presence of a highly characteristic DNA methylation profile in peripheral blood implicating 137 differentially methylated positions (DMP) in IBD, including VMP1/MIR21 (p = 9.11×10 − 15 ) and RPS6KA2 (6.43×10 − 13 ); with consistency seen across Scandinavia and UK. Cell of origin analysis preferentially implicated the monocyte lineage. Dysregulated loci demonstrate strong genetic influence, notably VMP1 (p = 1.53×10 − 15 ). Age acceleration is seen in IBD (coefficient 0.94, p < 2.2x10 − 16 ). Several immuno-active genes demonstrated highly significant correlations between methylation and gene expression in IBD, in particular OSM: IBD r -0.32, p 3.64×10 − 7 vs. non-IBD r -0.14, p = 0.77). Multi-omic integration of methylome, genome and transcriptome also implicate specific pathways that associate with immune activation, response and regulation at disease inception. At follow up, a signature of 3 DMPs ( TAP1, TESPA1, RPTOR ) associated with treatment escalation to biological agents or surgery (hazard ratio of 5.19 (CI:2.14–12.56, logrank p = 9.70×10 − 4 )." @default.
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• W3165194266 date "2021-05-27" @default.
• W3165194266 modified "2023-09-25" @default.
• W3165194266 title "Analysis of systemic epigenetic alterations in inflammatory bowel disease: defining geographical, genetic, and immune-inflammatory influences on the circulating methylome" @default.
• W3165194266 doi "https://doi.org/10.21203/rs.3.rs-537439/v1" @default.
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