{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:01:15Z","timestamp":1788573675832,"version":"build-2803163510"},"reference-count":70,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"Australian National Health and Medical Research Council (NHMRC)","doi-asserted-by":"publisher","award":["GNT1177194"],"award-info":[{"award-number":["GNT1177194"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometriosis is a chronic gynaecological disease characterised by endometrial-like tissue found external to the uterus. While several studies have reported strong evidence of a genetic contribution to the disease, studies on the environmental impact on endometriosis are limited. DNA methylation (DNAm) can be influenced by genetic and environmental factors and serves as a useful biological marker of the effects of genetic and environmental exposures on complex diseases. This study aims to develop a methylation risk score (MRS) for endometriosis to increase the power to detect DNAm signals associated with the disease and enhance our understanding of the pathogenesis of the disease. Endometrial methylation and genotype data from 318 controls and 590 cases were analysed. MRSs were developed using several different models. MRS performances were evaluated by splitting samples into training and test sets based on independent cohort institutions, and the area under the receiver-operator curve (AUC) was calculated. The maximum AUC obtained from the best-performing MRS is 0.6748, derived from 746 DNAm sites. The classification performance of MRS and polygenic risk score (PRS) combined was consistently higher than PRS alone. This study demonstrates that there are DNAm signals independent of common genetic variants associated with endometriosis.<\/jats:p>","DOI":"10.3390\/ijms26083760","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T08:09:17Z","timestamp":1744790957000},"page":"3760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Methylation Risk Score Modelling in Endometriosis: Evidence for Non-Genetic DNA Methylation Effects in a Case\u2013Control Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7835-0655","authenticated-orcid":false,"given":"Li Ying","family":"Thong","sequence":"first","affiliation":[{"name":"Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan F.","family":"McRae","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Sirota","sequence":"additional","affiliation":[{"name":"Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, CA 94158, USA"},{"name":"Department of Pediatrics, Division of Neonatology, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1677-0822","authenticated-orcid":false,"given":"Linda","family":"Giudice","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4140-8139","authenticated-orcid":false,"given":"Grant W.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2327-9465","authenticated-orcid":false,"given":"Sally","family":"Mortlock","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia"},{"name":"Australian Women and Girls\u2019 Health Research Centre, University of Queensland, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s41574-019-0245-z","article-title":"Rethinking mechanisms, diagnosis and management of endometriosis","volume":"15","author":"Chapron","year":"2019","journal-title":"Nat. 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