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. ; Lauc, G. ; Campbell, H. ; McGovern, D.P.B. ; Annese, V. ; Zoldoš, V. ; Permberton, I.K. ; Wuhrer, M. ; Kolarich, D. ; Fernandes, D.L. ; Theorodorou, E. ; Merrick, V. ; Spencer, D.I. ; Gardner, R.A. ; Doran, R. ; Shubhakar, A. ; Boyapati, R. ; Rudan, I. ; Lionetti, P. ; Akmacic, I.T. ; Krištic, J. ; Vuckovic, F. ; Štambuk, J. ; Novokmet, M. ; Pucic-Bakovic, M. ; Gornik, O. ; Andriulli, A. ; Cantoro, L. ; Sturniolo, G. ; Fiorino, G. ; Manetti, N. ; Latiano, A. ; Kohn, A. ; D''Incà, R. ; Danese, S. ; Arnott, I.D. ; Noble, C.L. ; Lees, C.W. ; Shand, A.G. ; Ho, G.T ; Dunlop, M.G. ; Murphy, L. ; Gibson, J. ; Evenden, L. ; Wrobel, N. ; Gilchrist, T. ; Fawkes, A. ; Kammeijer, G.S.M. ; Clerc, F. ; De Haan, N. ; Vojta, A. ; Samaržija, I. ; Markulin, D. ; Klasic, M. ; Dobrinic, P. ; Aulchenko, Y. ; Van, Den Heuve ; Jonkers, D. ; Pierik, M. ; Vatn, S. ; Ricanek, P. ; Jahnsen, J. ; You, P. ; Sølvernes, J. ; Frengen, A.B. ; Tannæs, T.M. ; Moen, A.E.F. ; Dahl, F.A. ; Lindstrøm, J.C. ; Ekeland, G.S. ; Detlie, T.E. ; Keita, A.V. ; Söderholm, J.D. ; Hjortswang, H. ; Halfvarson, J. ; Bergemalm, D. ; Gomollón, F. (Universidad de Zaragoza) ; D'Amato, M. ; Törkvist, L. ; Hjelm, F. ; Gullberg, M. ; Nordberg, N. ; Ocklind, A. ; Pettersson, E. ; Ekman, D. ; Sundell, M. ; Modig, E. ; Veillard, A.C. ; Schoemans, R. ; Poncelet, D. ; Sabatel, C. ; Gut, M. ; Bayes, M. ; Casén, C. ; Lindahl, T. ; Ciemniejewska, E. ; Vatn, M.H.

Resumen: 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.

Idioma: Inglés

DOI: 10.1038/ncomms13507

Año: 2016

Publicado en: Nature Communications 7 (2016), 13507 [14 pp]
ISSN: 2041-1723

Factor impacto JCR: 12.124 (2016)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 3 / 63 = 0.048 (2016) - Q1 - T1

Factor impacto SCIMAGO: 6.413 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1) - Physics and Astronomy (miscellaneous) (Q1) - Chemistry (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/EC/FP7/305479/EU/Diagnostic and prognostic biomarkers for inflammatory bowel diseaseIBD-BIOM/IBD-BIOM
Financiación: info:eu-repo/grantAgreement/EC/FP7/305676/EU/Inflammatory Bowel Disease CHARACTERization by a multi-modal integrated biomarker study/IBD-CHARACTER

Tipo y forma: Article (Published version)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)