1. Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
- Author
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KR O’Leary, Fernando Gomollón, Nicholas T. Ventham, Irena Trbojević Akmačić, Frano Vučković, Angie Fawkes, Fredrik A. Dahl, David C. Wilson, Jerko Štambuk, Fredrik Hjelm, Malcolm G. Dunlop, Simon Heath, Céline Sabatel, Eddie Modig, Noortje de Haan, Laura Cantoro, C. Casén, Maja Pučić-Baković, Jonas Christoffer Lindstrøm, Aina Elisabeth Fossum Moen, Mauro D'Amato, Dermot P.B. McGovern, Florent Clerc, Nicholas A. Kennedy, Anne Clémence Veillard, Daniel Bergemalm, Nicola Wrobel, Gunn S. Ekeland, Manfred Wuhrer, Colin L. Noble, Anna B. Frengen, Niklas Nordberg, Daisy Jonkers, Daryl L. Fernandes, Anette Ocklind, Dominique Poncelet, Rahul Kalla, Gionata Fiorino, Paolo Lionetti, Victoria Merrick, Petr Ricanek, Aleksandar Vojta, Alan G. Shand, Mikael Sundell, Johan D. Söderholm, Archana Shubhakar, Tim van den Heuve, Ivo Gut, Torbjørn Lindahl, Paula Dobrinić, Mislav Novokmet, G.C. Sturniolo, Natalia Manetti, Elaine R. Nimmo, Iain K. Permberton, Jasminka Krištić, Ray Boyapati, Igor Rudan, Olga Gornik, Anna Kohn, Leif Törkvist, Erik Pettersson, Gordan Lauc, Marieke Pierik, Ian D. Arnott, Lee Murphy, Monica Bayes, Ewa Ciemniejewska, Louise Evenden, Mats Gullberg, Jack Satsangi, Ivana Samaržija, Anna Latiano, Charlie W. Lees, Angelo Andriulli, Renata D'Incà, Jørgen Jahnsen, Renaud Schoemans, Panpan You, Yurii S. Aulchenko, Hazel E. Drummond, Gwo-Tzer Ho, Jonas Halfvarson, Vlatka Zoldoš, Tamara Gilchrist, Evropi Theorodorou, Marta Gut, Henrik Hjortswang, Daniel I. R. Spencer, Jude Gibson, Ray Doran, Silvio Danese, Simen Vatn, Alex Adams, Tone Møller Tannæs, Marija Klasić, Vito Annese, Daniel Ekman, Harry Campbell, Trond Espen Detlie, Dora Markulin, Åsa V. Keita, Guinevere S. M. Kammeijer, Janne Sølvernes, Morten H. Vatn, Richard A. Gardner, Daniel Kolarich, and Analytical Biochemistry
- Subjects
Epigenomics ,Male ,0301 basic medicine ,inflammatory bowel disease ,DNA methylation ,epigenetics ,General Physics and Astronomy ,Bioinformatics ,Inflammatory bowel disease ,Linkage Disequilibrium ,Epigenesis, Genetic ,Cohort Studies ,0302 clinical medicine ,Crohn Disease ,Genotype ,Promoter Regions, Genetic ,skin and connective tissue diseases ,Epigenesis ,Multidisciplinary ,Middle Aged ,Protein-Tyrosine Kinases ,030220 oncology & carcinogenesis ,Female ,Adult ,Science ,Quantitative Trait Loci ,Biology ,Polymorphism, Single Nucleotide ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,microRNA ,medicine ,Humans ,Genetic Predisposition to Disease ,Epigenetics ,Gene Expression Profiling ,Membrane Proteins ,General Chemistry ,Epigenome ,medicine.disease ,digestive system diseases ,MicroRNAs ,030104 developmental biology ,Case-Control Studies ,Colitis, Ulcerative ,Gene-Environment Interaction ,Gene expression ,sense organs - 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., Epigenetic perturbations may be an important factor in diseases where both genes and environment play a role. Here, Ventham and colleagues show that DNA methylation changes in inflammatory bowel disease are related to the underlying genotype, and are associated with cell-specific changes to gene expression.
- Published
- 2016