%0 Journal Article
%A Fraszczyk, Eliza
%A Spijkerman, Annemieke M W
%A Zhang, Yan
%A Brandmaier, Stefan
%A Day, Felix R
%A Zhou, Li
%A Wackers, Paul
%A Dollé, Martijn E T
%A Bloks, Vincent W
%A Gào, Xīn
%A Gieger, Christian
%A Kooner, Jaspal
%A Kriebel, Jennifer
%A Picavet, H Susan J
%A Rathmann, Wolfgang
%A Schöttker, Ben
%A Loh, Marie
%A Verschuren, W M Monique
%A van Vliet-Ostaptchouk, Jana V
%A Wareham, Nicholas J
%A Chambers, John C
%A Ong, Ken K
%A Grallert, Harald
%A Brenner, Hermann
%A Luijten, Mirjam
%A Snieder, Harold
%T Epigenome-wide association study of incident type 2 diabetes: a meta-analysis of five prospective European cohorts.
%J Diabetologia
%V 65
%N 5
%@ 0012-186X
%C Heidelberg
%I Springer
%M DKFZ-2022-00374
%P 763-776
%D 2022
%Z 2022 May;65(5):763-776
%X Type 2 diabetes is a complex metabolic disease with increasing prevalence worldwide. Improving the prediction of incident type 2 diabetes using epigenetic markers could help tailor prevention efforts to those at the highest risk. The aim of this study was to identify predictive methylation markers for incident type 2 diabetes by combining epigenome-wide association study (EWAS) results from five prospective European cohorts.We conducted a meta-analysis of EWASs in blood collected 7-10 years prior to type 2 diabetes diagnosis. DNA methylation was measured with Illumina Infinium Methylation arrays. A total of 1250 cases and 1950 controls from five longitudinal cohorts were included: Doetinchem, ESTHER, KORA1, KORA2 and EPIC-Norfolk. Associations between DNA methylation and incident type 2 diabetes were examined using robust linear regression with adjustment for potential confounders. Inverse-variance fixed-effects meta-analysis of cohort-level individual CpG EWAS estimates was performed using METAL. The methylGSA R package was used for gene set enrichment analysis. Confirmation of genome-wide significant CpG sites was performed in a cohort of Indian Asians (LOLIPOP, UK).The 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
%K Biomarkers (Other)
%K DNA methylation (Other)
%K Epigenetics (Other)
%K Epigenome-wide association studies (Other)
%K Meta-analysis (Other)
%K Prediction (Other)
%K Prospective studies (Other)
%K Type 2 diabetes (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35169870
%R 10.1007/s00125-022-05652-2
%U https://inrepo02.dkfz.de/record/178958