EBioMedicine (May 2024)
Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complicationsResearch in context
- Colette Christiansen,
- Louis Potier,
- Tiphaine C. Martin,
- Sergio Villicaña,
- Juan E. Castillo-Fernandez,
- Massimo Mangino,
- Cristina Menni,
- Pei-Chien Tsai,
- Purdey J. Campbell,
- Shelby Mullin,
- Juan R. Ordoñana,
- Olga Monteagudo,
- Perminder S. Sachdev,
- Karen A. Mather,
- Julian N. Trollor,
- Kirsi H. Pietilainen,
- Miina Ollikainen,
- Christine Dalgård,
- Kirsten Kyvik,
- Kaare Christensen,
- Jenny van Dongen,
- Gonneke Willemsen,
- Dorret I. Boomsma,
- Patrik K.E. Magnusson,
- Nancy L. Pedersen,
- Scott G. Wilson,
- Elin Grundberg,
- Tim D. Spector,
- Jordana T. Bell
Affiliations
- Colette Christiansen
- King's College London, UK; The Open University, Milton Keynes, UK; Corresponding author. King's College London, UK.
- Louis Potier
- APHP, Paris Cité University, INSERM, Paris, France
- Tiphaine C. Martin
- Icahn School of Medicine at Mount Sinai, USA
- Sergio Villicaña
- King's College London, UK
- Juan E. Castillo-Fernandez
- King's College London, UK
- Massimo Mangino
- King's College London, UK
- Cristina Menni
- King's College London, UK
- Pei-Chien Tsai
- 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
- Purdey J. Campbell
- Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
- Shelby Mullin
- Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA, 6009, Australia
- Juan R. Ordoñana
- University of Murcia, Spain
- Olga Monteagudo
- University of Murcia, Spain
- Perminder S. Sachdev
- University of New South Wales, Australia
- Karen A. Mather
- University of New South Wales, Australia
- Julian N. Trollor
- University of New South Wales, Australia
- Kirsi H. Pietilainen
- 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
- Miina Ollikainen
- Minerva Foundation Institute for Medical Research, Helsinki, Finland; Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Finland
- Christine Dalgård
- University of Southern Denmark, Denmark
- Kirsten Kyvik
- University of Southern Denmark, Denmark
- Kaare Christensen
- University of Southern Denmark, Denmark
- Jenny van Dongen
- Department of Biological Psychology, Vrije Universiteit Amsterdam, the Netherlands
- Gonneke Willemsen
- Department of Biological Psychology, Vrije Universiteit Amsterdam, the Netherlands
- Dorret I. Boomsma
- Department of Biological Psychology, Vrije Universiteit Amsterdam, the Netherlands
- Patrik K.E. Magnusson
- Karolinska Institute, Sweden
- Nancy L. Pedersen
- Karolinska Institute, Sweden
- Scott G. Wilson
- 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
- Elin Grundberg
- Children's Mercy Kansas City, USA
- Tim D. Spector
- King's College London, UK
- Jordana T. Bell
- King's College London, UK; Corresponding author.
- Journal volume & issue
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Vol. 103
p. 105096
Abstract
Summary: 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.
