{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T12:16:32Z","timestamp":1780056992480,"version":"3.54.0"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006095","name":"Helse S\u00f8r-\u00d8st RHF","doi-asserted-by":"publisher","award":["2021034"],"award-info":[{"award-number":["2021034"]}],"id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>An increasing body of evidence indicates altered DNA methylation in Parkinson's disease, yet the reproducibility and utility of such methylation changes are largely unexplored. We aimed to further elucidate the role of dysregulated DNA methylation in Parkinson's disease and to evaluate the biomarker potential of methylation\u2010based profiling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted an epigenome\u2010wide association study (EWAS) in whole blood, including 280 Parkinson's disease and 279 control participants from Oslo, Norway. Next, we took advantage of data from the Parkinson's Progression Markers Initiative (PPMI) and a previously published EWAS to conduct a whole blood EWAS meta\u2010analysis in Parkinson's disease, incorporating results from a total of 3068 participants. Finally, we generated multiple methylation\u2010based scores for each Oslo and PPMI participant and tested their association with disease status, individually and in a joint multiscore model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In EWAS meta\u2010analysis, we confirm <jats:italic>SLC7A11<\/jats:italic> hypermethylation and nominate a novel differentially methylated CpG near <jats:italic>LPIN1<\/jats:italic>. A joint multiscore model incorporating polygenic risk and methylation\u2010based estimates of epigenetic Parkinson's disease risk, smoking, and leukocyte proportions differentiated patients from control participants with an area under the receiver\u2010operator curve of 0.82 in the Oslo cohort and 0.65 in PPMI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our results highlight the power of DNA methylation profiling to capture multiple aspects of disease risk, indicating a biomarker potential for precision medicine in neurodegenerative disorders. The reproducibility of specific differentially methylated CpGs across data sets was limited but may improve if future studies are designed to account for disease stage and incorporate environmental exposure data.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52292","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T11:45:14Z","timestamp":1738755914000},"page":"701-713","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Epigenome\u2010wide association study, meta\u2010analysis, and multiscore profiling of whole blood in Parkinson's disease"],"prefix":"10.1002","volume":"12","author":[{"given":"Ingeborg Haugesag","family":"Lie","sequence":"first","affiliation":[{"name":"Department of Neurology Oslo University Hospital  Oslo Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela M. 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