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This study is the first to assess methylation signatures in IgG4-SC.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Whole blood DNA methylation profiling and genotyping was performed in 264 individuals; 47 with IgG4-SC, 65 with PSC, 64 with ulcerative colitis (UC), and 88 healthy controls. We identified 19 significant methylation differences between IgG4-SC and controls and 38 between PSC and controls. IgG4-SC and PSC shared 8 probes. Inflammatory genes (including <jats:italic>CEP97<\/jats:italic>, <jats:italic>IFNAR1<\/jats:italic>, <jats:italic>TXK<\/jats:italic>, <jats:italic>HERC6<\/jats:italic>, <jats:italic>C5orf36<\/jats:italic>, <jats:italic>PYY<\/jats:italic>, and <jats:italic>MTRNR2L1<\/jats:italic>) were predominantly involved in dysregulated methylation. Epigenetic age acceleration was observed in patients with IgG4-SC, but not in those with PSC or UC. meQTL analyses to identify genetic determinants of methylation revealed a strong human leucocyte antigen (HLA) signal in both PSC and IgG4-SC (<jats:italic>HLA-DQB2<\/jats:italic>, <jats:italic>HLA-DPA1<\/jats:italic>, <jats:italic>HLA-F<\/jats:italic> and <jats:italic>HLA-DRA<\/jats:italic>).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We identify novel epigenetic alterations in IgG4-SC and PSC, with biological age acceleration in IgG4-SC, providing insights into disease pathogenesis, and highlight the role of genetic variation especially within the HLA region in shaping the methylome.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13148-024-01803-x","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T12:49:28Z","timestamp":1737031768000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Epigenetic age acceleration and methylation differences in IgG4-related cholangitis and primary sclerosing cholangitis"],"prefix":"10.1186","volume":"17","author":[{"given":"Alexandra","family":"Noble","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Motta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Cabras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belen Moron","family":"Flores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Nowak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Glapa-Nowak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Geremia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Satsangi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Culver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"1803_CR1","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","volume":"15","author":"L Ferrucci","year":"2018","unstructured":"Ferrucci L, Fabbri E. 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