% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Sinke:282598,
      author       = {Sinke, Lucy and Delerue, Thomas and Wilson, Rory and Lu,
                      Xueling and Xia, Yujing and Costeira, Ricardo and Nasr, M
                      Kamal and Beekman, Marian and Franke, Lude and Zhernakova,
                      Alexandra and Fu, Jingyuan and Gieger, Christian and Herder,
                      Christian and Koenig, Wolfgang and Peters, Annette and
                      Ordovas, José M and Dörr, Marcus and Grabe, Hans J and
                      Nauck, Matthias and Bell, Jordana T and Teumer, Alexander
                      and Snieder, Harold and Waldenberger, Melanie and Slagboom,
                      P Eline and Heijmans, Bastiaan T},
      title        = {{DNA} methylation of genes involved in lipid metabolism
                      drives adiponectin levels and metabolic disease.},
      journal      = {Diabetologia},
      volume       = {69},
      number       = {1},
      issn         = {0012-186X},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DZNE-2025-01356},
      pages        = {127 - 145},
      year         = {2026},
      abstract     = {Despite playing critical roles in the pathophysiology of
                      type 2 diabetes and other metabolic disorders, the molecular
                      mechanisms underlying circulating adipokine levels remain
                      poorly understood. By identifying genomic regions involved
                      in the regulation of adipokine levels and adipokine-mediated
                      disease risk, we can improve our understanding of type 2
                      diabetes pathogenesis and inter-individual differences in
                      metabolic risk.We conducted an epigenome-wide meta-analysis
                      of associations between serum adiponectin (n=2791) and
                      leptin (n=3661) and leukocyte DNA methylation at over
                      400,000 CpG sites across five European cohorts. The
                      resulting methylation signatures were followed up using
                      functional genomics, integrative analyses and causal
                      inference methods.Our findings revealed robust associations
                      with adiponectin at 73 CpGs and leptin at 211 CpGs. Many of
                      the identified sites were also associated with risk factors
                      for the metabolic syndrome and located in enhancers close to
                      relevant transcription factor binding sites. Integrative
                      analyses additionally linked 35 of the
                      adiponectin-associated CpGs to the expression of 46 genes,
                      and 100 of the leptin-associated CpGs to the expression of
                      151 genes, with implicated genes enriched for lipid
                      transport (e.g. ABCG1), metabolism (e.g. CPT1A) and
                      biosynthesis (e.g. DHCR24). Bidirectional two-sample
                      Mendelian randomisation further identified two specific CpG
                      sites as plausible drivers of both adiponectin levels and
                      metabolic health: one annotated to ADIPOQ, the gene encoding
                      adiponectin; and another linked to the expression of SREBF1,
                      an established modifier of type 2 diabetes risk known to
                      exert its effects via adiponectin.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.},
      keywords     = {Humans / Adiponectin: blood / Adiponectin: genetics /
                      Adiponectin: metabolism / DNA Methylation: genetics / Lipid
                      Metabolism: genetics / Diabetes Mellitus, Type 2: genetics /
                      Diabetes Mellitus, Type 2: metabolism / Leptin: blood /
                      Leptin: genetics / CpG Islands: genetics / Metabolic
                      Diseases: genetics / Metabolic Diseases: metabolism /
                      Genome-Wide Association Study / Female / Male / Adiponectin
                      (Other) / Causal inference (Other) / Epigenomics (Other) /
                      Leptin (Other) / Lipid metabolism (Other) / Meta-analysis
                      (Other) / Metabolic health (Other) / Type 2 diabetes (Other)
                      / Adiponectin (NLM Chemicals) / Leptin (NLM Chemicals)},
      cin          = {AG Grabe},
      ddc          = {610},
      cid          = {I:(DE-2719)5000001},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41057690},
      doi          = {10.1007/s00125-025-06549-6},
      url          = {https://pub.dzne.de/record/282598},
}