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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 (\n                    <jats:italic>RPS6KA2<\/jats:italic>\n                    ) and DMRs (\n                    <jats:italic>VMP1, ITGB2<\/jats:italic>\n                    and\n                    <jats:italic>TXK<\/jats:italic>\n                    ) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci;\n                    <jats:italic>VMP1\/microRNA-21<\/jats:italic>\n                    methylation associates with two polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data shows that IBD-associated hypermethylation within the\n                    <jats:italic>TXK<\/jats:italic>\n                    promoter region negatively correlates with gene expression in whole-blood and CD8\n                    <jats:sup>+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/ncomms13507","type":"journal-article","created":{"date-parts":[[2016,11,25]],"date-time":"2016-11-25T07:18:06Z","timestamp":1480058286000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":256,"title":["Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease"],"prefix":"10.1038","volume":"7","author":[{"given":"N. 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