Longitudinal association between DNA methylation and type 2 diabetes: findings from the KORA F4/FF4 study
An erratum to this article was published (Cardiovasc Diabetol, 14 Jun 2025 ↗)
Authors' conclusion
Our study identified novel differentially methylated loci linked to T2D as well as to changes in diabetes status through a longitudinal approach. We report CpG sites with different rates of annual methylation change and demonstrate that DNA methylation associated with T2D is linked to following transcriptional differences. These findings provide new insights into the molecular mechanisms of diabetes development.
Study context
- Population
- Participants of the KORA F4 and FF4 studies (Augsburg region) with leucocyte DNA methylation measured at least once across two visits3,501 observations
- Participants
- 2,556 participants
- Exposure
- DNA methylation by diabetes status and glycaemic traits
- Outcome
- CpG sites associated with T2D
Methodological detailsepigenome-wide association, two time-points approximately seven years apart, linear mixed-effects models, Leucocyte DNA methylation assessed with Illumina EPIC and 450K arrays
- Epigenome-wide association
- Two time-points approximately seven years apart
- Linear mixed-effects models
- Leucocyte DNA methylation assessed with Illumina EPIC and 450K arrays
Main finding
As reported in the abstract
Sites associated with T2D (incl. Thioredoxin-interacting protein (TXNIP), ABCG1)
64
Novel sites associated with T2D
15
CpG sites with different rates of annual methylation change between normal glucose tolerance (NGT) and T2D
8
CpG sites linked to progression from NGT to prediabetes or T2D (incl. MAN2A2, CPT1A)
7
Observational data: associations, not effects.
Further findings
Longitudinal associations of methylation with glycaemic traits
- Sites associated with fasting plasma glucose (FPG)
- 128
- Sites associated with hemoglobin A1c (HbA1c)
- 41
- Sites associated with homoeostasis model assessment of insulin resistance (HOMA-IR)
- 57
CpG-transcript pairs in whole blood
- CpG-transcript pairs
- 104
- Unique CpG sites
- 40
- Unique gene transcripts
- 96
Original publication
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