Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease

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...

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Autores: Ventham, N. T., Kennedy, N. A., Adams, A. T., Kalla, Rahul, Heath, Simon, O'Leary, K. R., Drummond, H., IBD BIOM consortium, IBD CHARACTER consortium, Wilson, D. C., Gut, Ivo Glynne, Nimmo, E. R., Satsangi, Jack
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/27946
Acceso en línea:http://hdl.handle.net/10230/27946
http://dx.doi.org/10.1038/ncomms13507
Access Level:acceso abierto
Palabra clave:DNA methylation
Gene expression
Inflammatory bowel disease
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spelling Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel diseaseVentham, N. T.Kennedy, N. A.Adams, A. T.Kalla, RahulHeath, SimonO'Leary, K. R.Drummond, H.IBD BIOM consortiumIBD CHARACTER consortiumWilson, D. C.Gut, Ivo GlynneNimmo, E. R.Satsangi, JackDNA methylationGene expressionInflammatory bowel diseaseEpigenetic 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.Nature Publishing Group201720172016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/27946http://dx.doi.org/10.1038/ncomms13507reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNature Communications. 2016; 7: 13507© 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/http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/279462026-06-12T07:21:37Z
dc.title.none.fl_str_mv Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
title Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
spellingShingle Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
Ventham, N. T.
DNA methylation
Gene expression
Inflammatory bowel disease
title_short Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
title_full Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
title_fullStr Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
title_full_unstemmed Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
title_sort Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
dc.creator.none.fl_str_mv Ventham, N. T.
Kennedy, N. A.
Adams, A. T.
Kalla, Rahul
Heath, Simon
O'Leary, K. R.
Drummond, H.
IBD BIOM consortium
IBD CHARACTER consortium
Wilson, D. C.
Gut, Ivo Glynne
Nimmo, E. R.
Satsangi, Jack
author Ventham, N. T.
author_facet Ventham, N. T.
Kennedy, N. A.
Adams, A. T.
Kalla, Rahul
Heath, Simon
O'Leary, K. R.
Drummond, H.
IBD BIOM consortium
IBD CHARACTER consortium
Wilson, D. C.
Gut, Ivo Glynne
Nimmo, E. R.
Satsangi, Jack
author_role author
author2 Kennedy, N. A.
Adams, A. T.
Kalla, Rahul
Heath, Simon
O'Leary, K. R.
Drummond, H.
IBD BIOM consortium
IBD CHARACTER consortium
Wilson, D. C.
Gut, Ivo Glynne
Nimmo, E. R.
Satsangi, Jack
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DNA methylation
Gene expression
Inflammatory bowel disease
topic DNA methylation
Gene expression
Inflammatory bowel disease
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/27946
http://dx.doi.org/10.1038/ncomms13507
url http://hdl.handle.net/10230/27946
http://dx.doi.org/10.1038/ncomms13507
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nature Communications. 2016; 7: 13507
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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