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environmental risk factors contributing to its prevalence. Epigenetic mechanisms related to changes in DNA methylation (DNAm), may also contribute to T2D risk, but larger studies are required to discover novel markers, and to confirm existing ones.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We performed a large meta-analysis of individual epigenome-wide association studies (EWAS) of prevalent T2D conducted in four European studies using peripheral blood DNAm. Analysis of differentially methylated regions (DMR) was also undertaken, based on the meta-analysis results. We found three novel CpGs associated with prevalent T2D in Europeans at cg00144180 (<jats:italic>HDAC4<\/jats:italic>), cg16765088 (near <jats:italic>SYNM<\/jats:italic>) and cg24704287 (near <jats:italic>MIR23A<\/jats:italic>) and confirmed three CpGs previously identified (mapping to <jats:italic>TXNIP<\/jats:italic>, <jats:italic>ABCG1<\/jats:italic> and <jats:italic>CPT1A<\/jats:italic>). We also identified 77 T2D associated DMRs, most of them hypomethylated in T2D cases versus controls. In adjusted regressions among diabetic-free participants in ALSPAC, we found that all six CpGs identified in the meta-EWAS were associated with white cell-types. We estimated that these six CpGs captured 11% of the variation in T2D, which was similar to the variation explained by the model including only the common risk factors of BMI, sex, age and smoking (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u200910.6%).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study identifies novel loci associated with T2D in Europeans. We also demonstrate associations of the same loci with other traits. Future studies should investigate if our findings are generalizable in non-European populations, and potential roles of these epigenetic markers in T2D etiology or in determining long term consequences of T2D.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13148-021-01027-3","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T13:03:23Z","timestamp":1614085403000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-918X","authenticated-orcid":false,"given":"Diana L.","family":"Juvinao-Quintero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo E.","family":"Marioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Ochoa-Rosales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom C.","family":"Russ","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"Deary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce B. 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Ethics permission for the LBC1936 was obtained from the Multi-Centre Research Ethics Committee for Scotland (Wave 1: MREC\/01\/0\/56), the Lothian Research Ethics Committee (Wave 1: LREC\/2003\/2\/29). Written informed consent was obtained from all subjects. The Rotterdam Study has been approved by the Medical Ethics Committee of the Erasmus MC (registration number MEC 02.1015) and by the Dutch Ministry of Health, Welfare and Sport (Population Screening Act WBO, license number 1071272-159521-PG). 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