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
DOIAbstract
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 signalli...
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