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

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Ventham, N. T.Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK (author)

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

Article/chapterEnglish2016

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2016-11-25
London, United Kingdom :Nature Publishing Group,2016
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LIBRIS-ID:oai:DiVA.org:oru-55712
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-55712URI
https://doi.org/10.1038/ncomms13507DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:134635416URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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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.

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NATURVETENSKAP Biologi Genetik hsv//swe
NATURAL SCIENCES Biological Sciences Genetics hsv//eng

Added entries (persons, corporate bodies, meetings, titles ...)

Kennedy, N. A.Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK (author)
Adams, A. T.Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK (author)
Kalla, R.Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK (author)
Heath, S.CNAG-CRG, Centro Nacional de Análisis Genómico, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain (author)
O'Leary, K. R.Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK (author)
Drummond, H.Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK (author)
IBD CHARACTER, consortium (author)
Wilson, D. C.Department of Child Life and Health, University of Edinburgh, Edinburgh, UK (author)
Gut, I. G.CNAG-CRG, Centro Nacional de Análisis Genómico, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain (author)
Nimmo, E. R.Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK (author)
Satsangi, J.Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK (author)
Halfvarson, Jonas,1970-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden(Swepub:oru)jshn (contributor)
Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UKCNAG-CRG, Centro Nacional de Análisis Genómico, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain (creator_code:org_t)

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In:Nature CommunicationsLondon, United Kingdom : Nature Publishing Group72041-1723

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By the author/editor: Ventham, N. T.; Kennedy, N. A.; Adams, A. T.; Kalla, R.; Heath, S.; O'Leary, K. R.; show more...; Drummond, H.; IBD CHARACTER, c ...; Wilson, D. C.; Gut, I. G.; Nimmo, E. R.; Satsangi, J.; Halfvarson, Jona ...; show less...

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Genetics

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By the university: Örebro University; Karolinska Institutet

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