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EPIGENETIC ALTERATI...
EPIGENETIC ALTERATIONS IN IBD : DEFINING GEOGRAPHICAL, GENETIC, AND IMMUNEIN-FLAMMATORY INFLUENCES ON THE CIRCULATING METHYLOME
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- Kalla, Rahul (author)
- University of Edinburgh, Edinburgh, UK
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- Adams, Alex (author)
- University of Oxford, Oxford, UK
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- Nowak, Jan (author)
- Poznan University of Medical Sciences, Poznan, Poland
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- Bergemalm, Daniel, 1977- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län
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- Vatn, Simen (author)
- University of Oslo, Oslo, Norway
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- Ventham, Nicholas (author)
- University of Edinburgh, Edinburgh, UK
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- Kennedy, Nicholas (author)
- University of Exeter, Exeter, UK
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- Ricanek, Petr (author)
- University of Oslo, Oslo, Norway
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- Lindström, Jonas (author)
- University of Oslo, Oslo, Norway
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- Pierik, Marieke (author)
- Maastricht University Medical Centre, Maastricht, Netherlands
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- D'Amato, Mauro (author)
- BioCruces Health Research Institute and IKERBASQUE, Bilbao, Spain; Monash University, Melbourne, Australia
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- Gomollon, Fernando (author)
- HCU ‘Lozano Blesa,’ IIS Aragón, Zaragosa, Spain
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- Olbjorn, Christine (author)
- University of Oslo, Oslo, Norway
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- Richmond, Rebecca (author)
- University of Bristol, Bristol, UK
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- Relton, Caroline (author)
- University of Bristol, Bristol, UK
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- Söderholm, Johan (author)
- University of Linköping, Linköping, Sweden
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- Jahnsen, Jorgen (author)
- University of Oslo, Oslo, Norway; Akershus University Hospital, Akershus, Norway
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- Vatn, Morten (author)
- University of Oslo, Oslo, Norway
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- Halfvarson, Jonas, 1970- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper
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- Satsangi, Jack (author)
- University of Oxford, Oxford, UK
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(creator_code:org_t)
- BMJ Publishing Group Ltd, 2021
- 2021
- English.
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In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:Suppl. 4, s. A5-A5
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
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- Introduction: DNA methylation may provide critical insights into gene-environment interactions in inflammatory bowel disease (IBD).Methods: Using the multi-centre IBD Character inception cohort (295 controls, 154 CD, 161 UC, 28 IBD-U), epigenome-wide methylation was profiled using Illumina HumanMethylation450 platform. Differentially methylated position analysis was performed using age, sex and cell proportions as covariates. Integration of paired genomic and transcriptomic layers was done with Multi-Omics Factor Analysis v2 (MOFA). Unsupervised principal component analyses were performed to examine correlates of treatment escalation and clinical predictors of disease severity.Results: We report 137 differentially methylated positions (DMP) in whole blood 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 identified 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).Conclusion: This study highlights the stability of the IBD-specific circulating methylome across regions with shared ancestry. Through integrative multi-omic analyses we identify key pro-inflammatory genes that are upregulated in IBD at inception. Furthermore, differential methylation within certain genes such as TAP1 associate with disease course over time.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
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- vet (subject category)
- art (subject category)
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Gut
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- By the author/editor
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Kalla, Rahul
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Adams, Alex
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Nowak, Jan
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Bergemalm, Danie ...
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Vatn, Simen
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Ventham, Nichola ...
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Kennedy, Nichola ...
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Ricanek, Petr
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Lindström, Jonas
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Pierik, Marieke
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D'Amato, Mauro
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Gomollon, Fernan ...
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Olbjorn, Christi ...
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Richmond, Rebecc ...
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Relton, Caroline
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Söderholm, Johan
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Jahnsen, Jorgen
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Vatn, Morten
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Halfvarson, Jona ...
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Satsangi, Jack
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Gastroenterology ...
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Gut
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Örebro University