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Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications.
Christiansen, Colette; Potier, Louis; Martin, Tiphaine C; Villicaña, Sergio; Castillo-Fernandez, Juan E; Mangino, Massimo; Menni, Cristina; Tsai, Pei-Chien; Campbell, Purdey J; Mullin, Shelby; Ordoñana, Juan R; Monteagudo, Olga; Sachdev, Perminder S; Mather, Karen A; Trollor, Julian N; Pietilainen, Kirsi H; Ollikainen, Miina; Dalgård, Christine; Kyvik, Kirsten; Christensen, Kaare; van Dongen, Jenny; Willemsen, Gonneke; Boomsma, Dorret I; Magnusson, Patrik K E; Pedersen, Nancy L; Wilson, Scott G; Grundberg, Elin; Spector, Tim D; Bell, Jordana T.
Afiliação
  • Christiansen C; King's College London, UK; The Open University, Milton Keynes, UK. Electronic address: colette.christiansen@open.ac.uk.
  • Potier L; APHP, Paris Cité University, INSERM, Paris, France.
  • Martin TC; Icahn School of Medicine at Mount Sinai, USA.
  • Villicaña S; King's College London, UK.
  • Castillo-Fernandez JE; King's College London, UK.
  • Mangino M; King's College London, UK.
  • Menni C; King's College London, UK.
  • Tsai PC; King's College London, UK; Department of Biomedical Sciences, Chang Gung University, Taoyuan City, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
  • Campbell PJ; Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
  • Mullin S; Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA, 6009, Australia.
  • Ordoñana JR; University of Murcia, Spain.
  • Monteagudo O; University of Murcia, Spain.
  • Sachdev PS; University of New South Wales, Australia.
  • Mather KA; University of New South Wales, Australia.
  • Trollor JN; University of New South Wales, Australia.
  • Pietilainen KH; Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Finland; HealthyWeightHub, Abdominal Center, Helsinki University Hospital and University of Helsinki, Finland.
  • Ollikainen M; Minerva Foundation Institute for Medical Research, Helsinki, Finland; Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Finland.
  • Dalgård C; University of Southern Denmark, Denmark.
  • Kyvik K; University of Southern Denmark, Denmark.
  • Christensen K; University of Southern Denmark, Denmark.
  • van Dongen J; Department of Biological Psychology, Vrije Universiteit Amsterdam, the Netherlands.
  • Willemsen G; Department of Biological Psychology, Vrije Universiteit Amsterdam, the Netherlands.
  • Boomsma DI; Department of Biological Psychology, Vrije Universiteit Amsterdam, the Netherlands.
  • Magnusson PKE; Karolinska Institute, Sweden.
  • Pedersen NL; Karolinska Institute, Sweden.
  • Wilson SG; King's College London, UK; Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA, 6009, Australia.
  • Grundberg E; Children's Mercy Kansas City, USA.
  • Spector TD; King's College London, UK.
  • Bell JT; King's College London, UK. Electronic address: jordana.bell@kcl.ac.uk.
EBioMedicine ; 103: 105096, 2024 May.
Article em En | MEDLINE | ID: mdl-38574408
ABSTRACT

BACKGROUND:

Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression.

METHODS:

We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites.

FINDINGS:

We find and replicate 3 previously unreported T2D differentially methylated CpG positions (T2D-DMPs) at FDR 5% in RGL3, NGB and OTX2, and 20 signals at FDR 25%, of which 14 replicated. Integrating genetic variation and T2D-discordant monozygotic twin analyses, we identify both genetic-based and genetic-independent T2D-DMPs. The signals annotate to genes with established GWAS and EWAS links to T2D and its complications, including blood pressure (RGL3) and eye disease (OTX2).

INTERPRETATION:

The results help to improve our understanding of T2D disease pathogenesis and progression and may provide biomarkers for its complications.

FUNDING:

Funding acknowledgements for each cohort can be found in the Supplementary Note.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ilhas de CpG / Metilação de DNA / Diabetes Mellitus Tipo 2 Limite: Female / Humans / Male / Middle aged Idioma: En Revista: EBioMedicine Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ilhas de CpG / Metilação de DNA / Diabetes Mellitus Tipo 2 Limite: Female / Humans / Male / Middle aged Idioma: En Revista: EBioMedicine Ano de publicação: 2024 Tipo de documento: Article