Fraszczyk, ElizaSpijkerman, Annemieke M WZhang, YanBrandmaier, StefanDay, Felix RZhou, LiWackers, PaulDollé, Martijn E TBloks, Vincent WGào, XīnGieger, ChristianKooner, JaspalKriebel, JenniferPicavet, H Susan JRathmann, WolfgangSchöttker, BenLoh, MarieVerschuren, W M Moniquevan Vliet-Ostaptchouk, Jana VWareham, Nicholas JChambers, John COng, Ken KGrallert, HaraldBrenner, HermannLuijten, MirjamSnieder, Harold2022-03-282022-03-282022-02-153516987010.1007/s00125-022-05652-2http://hdl.handle.net/10029/625663The meta-analysis identified 76 CpG sites that were differentially methylated in individuals with incident type 2 diabetes compared with control individuals (p values <1.1 × 10-7). Sixty-four out of 76 (84.2%) CpG sites were confirmed by directionally consistent effects and p values <0.05 in an independent cohort of Indian Asians. However, on adjustment for baseline BMI only four CpG sites remained genome-wide significant, and addition of the 76 CpG methylation risk score to a prediction model including established predictors of type 2 diabetes (age, sex, BMI and HbA1c) showed no improvement (AUC 0.757 vs 0.753). Gene set enrichment analysis of the full epigenome-wide results clearly showed enrichment of processes linked to insulin signalling, lipid homeostasis and inflammation.en© 2022. The Author(s).BiomarkersDNA methylationEpigeneticsEpigenome-wide association studiesMeta-analysisPredictionProspective studiesType 2 diabetesArticle1432-0428Diabetologia 2022; 65(5):763-776