Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
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- dc.contributor.author Ventham, N. T.ca
- dc.contributor.author Kennedy, N. A.ca
- dc.contributor.author Adams, A. T.ca
- dc.contributor.author Kalla, Rahulca
- dc.contributor.author Heath, Simonca
- dc.contributor.author O'Leary, K. R.ca
- dc.contributor.author Drummond, H.ca
- dc.contributor.author IBD BIOM consortiumca
- dc.contributor.author IBD CHARACTER consortiumca
- dc.contributor.author Wilson, D. C.ca
- dc.contributor.author Gut, Ivo Glynneca
- dc.contributor.author Nimmo, E. R.ca
- dc.contributor.author Satsangi, Jackca
- dc.date.accessioned 2017-01-20T12:11:39Z
- dc.date.available 2017-01-20T12:11:39Z
- dc.date.issued 2016ca
- dc.description.abstract Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2 and TXK) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with two polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data shows that IBD-associated hypermethylation within the TXK promoter region negatively correlates with gene expression in whole-blood and CD8+ T cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD relate to underlying genotype and associate with cell-specific alteration in gene expression.
- dc.format.mimetype application/pdfca
- dc.identifier.citation Ventham NT, Kennedy NA, Adams AT, Kalla R, Heath S, O'Leary KR, Drummond H, IBD BIOM consortium, IBD CHARACTER consortium, Wilson DC, Gut IG, Nimmo ER, Satsangi J. Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease. Nature Communications. 2016; 7: 13507. DOI: 10.1038/ncomms13507ca
- dc.identifier.doi http://dx.doi.org/10.1038/ncomms13507
- dc.identifier.issn 2041-1723ca
- dc.identifier.uri http://hdl.handle.net/10230/27946
- dc.language.iso engca
- dc.publisher Nature Publishing Groupca
- dc.relation.ispartof Nature Communications. 2016; 7: 13507
- dc.rights © Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword DNA methylation
- dc.subject.keyword Gene expression
- dc.subject.keyword Inflammatory bowel disease
- dc.title Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel diseaseca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca