DNA methylation of genes involved in lipid metabolism drives adiponectin levels and metabolic disease
Authors' conclusion
Taken together, these large-scale and integrative analyses uncovered links between adipokines and widespread, yet functionally specific, differences in regulation of genes with a central role in type 2 diabetes and its risk factors.
Study context
- Population
- Five European cohorts; leukocyte DNA methylation at >400,000 CpG sites, with serum adiponectin and leptin5 European cohorts
- Outcome
- Associations of serum adiponectin and leptin with leukocyte DNA methylation
Methodological detailsfive European cohorts, functional genomics, integrative analyses, bidirectional two-sample Mendelian randomisation
- Five European cohorts
- Functional genomics
- Integrative analyses
- Bidirectional two-sample Mendelian randomisation
Pooled result
As reported in the abstract
CpGs associated with adipokine levels
CpGs associated with adiponectin (n=2791)
73
CpGs associated with leptin (n=3661)
211
Further pooled results
Integrative analyses: CpG–gene expression links
- Adiponectin-associated CpGs linked to expression of 46 genes
- 35
- Leptin-associated CpGs linked to expression of 151 genes
- 100
- Implicated genes enriched for lipid transport (e.g. ABCG1), metabolism (e.g. CPT1A) and biosynthesis (e.g. DHCR24)
Bidirectional two-sample Mendelian randomisation
- CpG sites identified as plausible drivers of both adiponectin levels and metabolic health: one annotated to ADIPOQ, one linked to SREBF1 expression
- 2
Original publication
DNA methylation of genes involved in lipid metabolism drives adiponectin levels and metabolic disease. Diabetologia. Published 8 October 2025. doi:10.
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