TY  - JOUR
AU  - Fraszczyk, Eliza
AU  - Spijkerman, Annemieke M W
AU  - Zhang, Yan
AU  - Brandmaier, Stefan
AU  - Day, Felix R
AU  - Zhou, Li
AU  - Wackers, Paul
AU  - Dollé, Martijn E T
AU  - Bloks, Vincent W
AU  - Gào, Xīn
AU  - Gieger, Christian
AU  - Kooner, Jaspal
AU  - Kriebel, Jennifer
AU  - Picavet, H Susan J
AU  - Rathmann, Wolfgang
AU  - Schöttker, Ben
AU  - Loh, Marie
AU  - Verschuren, W M Monique
AU  - van Vliet-Ostaptchouk, Jana V
AU  - Wareham, Nicholas J
AU  - Chambers, John C
AU  - Ong, Ken K
AU  - Grallert, Harald
AU  - Brenner, Hermann
AU  - Luijten, Mirjam
AU  - Snieder, Harold
TI  - Epigenome-wide association study of incident type 2 diabetes: a meta-analysis of five prospective European cohorts.
JO  - Diabetologia
VL  - 65
IS  - 5
SN  - 0012-186X
CY  - Heidelberg
PB  - Springer
M1  - DKFZ-2022-00374
SP  - 763-776
PY  - 2022
N1  - 2022 May;65(5):763-776
AB  - 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
KW  - Biomarkers (Other)
KW  - DNA methylation (Other)
KW  - Epigenetics (Other)
KW  - Epigenome-wide association studies (Other)
KW  - Meta-analysis (Other)
KW  - Prediction (Other)
KW  - Prospective studies (Other)
KW  - Type 2 diabetes (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:35169870
DO  - DOI:10.1007/s00125-022-05652-2
UR  - https://inrepo02.dkfz.de/record/178958
ER  -