Novel epigenetic marks of insulin resistance trajectories in a longitudinal study of childhood obesity
Authors' conclusion
This longitudinal EWAS in children with obesity shows that specific blood DNA methylation signatures mirror IR status and track its evolution across the pubertal transition, with opposing methylation trajectories distinguishing improving from persistent IR.
Study context
- Population
- Children with obesity followed from pre-pubertal to pubertal stage (PUBMEP study); Insulin resistance (IR) defined by sex- and pubertal stage specific HOMA-IR cut-offslongitudinal core
- Participants
- 90 children
- Outcome
- Association between IR status/trajectories and blood DNA methylation
- Follow-up
- Pre-pubertal to pubertal stages
Methodological detailscross-sectional analyses, mQTL analyses, Cross-sectional sets: 99 pre-pubertal and 129 pubertal participants
- Cross-sectional analyses
- mQTL analyses
- Cross-sectional sets: 99 pre-pubertal and 129 pubertal participants
Main finding
As reported in the abstract
CpG sites associated with obesity-associated IR across pubertal transition
- CpG sites significant after global FDR correction (FDR < 0.05)
- 120
Observational data: associations, not effects.
Further findings
Candidate loci and cardiometabolic traits · pubertal stage
- Methylation at CpG sites in SLC2A9, PEPD, TSC2, EGLN3, EHD2 and VASN consistently associated with pubertal HOMA-IR z-score and, for several loci, adiposity and blood pressure
mQTL look-up in GoDMC
- Cis SNP–CpG associations
- 25
- CpG sites (of 120) with cis mQTL, incl. SLC2A9 and TSC2
- 20
Original publication
Novel epigenetic marks of insulin resistance trajectories in a longitudinal study of childhood obesity. Cardiovasc Diabetol. Published 24 February 2026. doi:10.
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