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Although recent studies have implicated epigenetic variation in common neurodegenerative disorders, no study has yet explored their role in human prion diseases. Here we profiled genome-wide blood DNA methylation in the most common human prion disease, sporadic Creutzfeldt\u2013Jakob disease (sCJD). Our case\u2013control study (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009219), when accounting for differences in cell type composition between individuals, identified 38 probes at genome-wide significance (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20091.24\u2009\u00d7\u200910\n                    <jats:sup>\u20137<\/jats:sup>\n                    ). Nine of these sites were taken forward in a replication study, performed in an independent case\u2013control (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009186) cohort using pyrosequencing. Sites in or close to\n                    <jats:italic>FKBP5, AIM2<\/jats:italic>\n                    (2 probes)\n                    <jats:italic>, UHRF1, KCNAB2<\/jats:italic>\n                    successfully replicated. The blood-based DNA methylation signal was tissue- and disease-specific, in that the replicated probe signals were unchanged in case\u2013control studies using sCJD frontal-cortex (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200984), blood samples from patients with Alzheimer\u2019s disease, and from inherited and acquired prion diseases. Machine learning algorithms using blood DNA methylation array profiles accurately distinguished sCJD patients and controls. Finally, we identified sites whose methylation levels associated with prolonged survival in sCJD patients. Altogether, this study has identified a peripheral DNA methylation signature of sCJD with a variety of potential biomarker applications.\n                  <\/jats:p>","DOI":"10.1007\/s00401-020-02224-9","type":"journal-article","created":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T23:47:28Z","timestamp":1599868048000},"page":"863-879","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Altered DNA methylation profiles in blood from patients with sporadic Creutzfeldt\u2013Jakob disease"],"prefix":"10.1007","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6365-291X","authenticated-orcid":false,"given":"Luke C.","family":"Dabin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Guntoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"B\u00e9licard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam R.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca G.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Raybould","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Schott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7570-6065","authenticated-orcid":false,"given":"Katie","family":"Lunnon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sarkies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Mead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7868-9923","authenticated-orcid":false,"given":"Emmanuelle","family":"Vir\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,12]]},"reference":[{"key":"2224_CR1","unstructured":"Abadi M (2015) TensorFlow: large-scale machine learning on heterogeneous distributed systems. arXiv. arXiv:1603.04467"},{"key":"2224_CR2","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s13148-019-0672-7","volume":"11","author":"M Altuna","year":"2019","unstructured":"Altuna M, Urdanoz-Casado A, Sanchez-Ruiz de Gordoa J, Zelaya MV, Labarga A, Lepesant JMJ et al (2019) DNA methylation signature of human hippocampus in Alzheimer's disease is linked to neurogenesis. 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