Epigenome-wide association study of incident type 2 diabetes: a meta-analysis of five prospective European cohorts.
Fraszczyk, Eliza; Spijkerman, Annemieke M W; Zhang, Yan; Brandmaier, Stefan; Day, Felix R; Zhou, Li; Wackers, Paul; Dollé, Martijn E T; Bloks, Vincent W; Gào, Xīn; Gieger, Christian; Kooner, Jaspal; Kriebel, Jennifer; Picavet, H Susan J; Rathmann, Wolfgang; Schöttker, Ben; Loh, Marie; Verschuren, W M Monique; van Vliet-Ostaptchouk, Jana V; Wareham, Nicholas J; Chambers, John C; Ong, Ken K; Grallert, Harald; Brenner, Hermann; Luijten, Mirjam; Snieder, Harold
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Type
Article
Language
en
Date
2022-02-15
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Title
Epigenome-wide association study of incident type 2 diabetes: a meta-analysis of five prospective European cohorts.
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Diabetologia 2022; 65(5):763-776
Abstract
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%) 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.