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

Ventham, N T ; Kennedy, N A ; Adams, A T ; Kalla, R ; Heath, S ; O'Leary, K R ; Drummond, H ; Wilson, D C ; Gut, I G ; Nimmo, E R ; Satsangi, J

Nature communications, 2016-11, Vol.7 (1), p.13507-13507, Article 13507 [Peer Reviewed Journal]

England: Nature Publishing Group

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Title:
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
Author: Ventham, N T ; Kennedy, N A ; Adams, A T ; Kalla, R ; Heath, S ; O'Leary, K R ; Drummond, H ; Wilson, D C ; Gut, I G ; Nimmo, E R ; Satsangi, J
Subjects: Adult ; Case-Control Studies ; Cohort Studies ; Colitis, Ulcerative - blood ; Colitis, Ulcerative - genetics ; Crohn Disease - blood ; Crohn Disease - genetics ; DNA Methylation - genetics ; Epigenesis, Genetic ; Epigenomics - methods ; Female ; Gene Expression Profiling - methods ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Genotype ; Humans ; Inflammatory bowel disease ; Linkage Disequilibrium ; Male ; Medicin och hälsovetenskap ; Membrane Proteins - genetics ; MicroRNAs - genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Protein-Tyrosine Kinases - genetics ; Quantitative Trait Loci - genetics
Is Part Of: Nature communications, 2016-11, Vol.7 (1), p.13507-13507, Article 13507
Notes: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
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.
Publisher: England: Nature Publishing Group
Language: English

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

Ventham, N T ; Kennedy, N A ; Adams, A T ; Kalla, R ; Heath, S ; O'Leary, K R ; Drummond, H ; Wilson, D C ; Gut, I G ; Nimmo, E R ; Satsangi, J

England: Nature Publishing Group

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