Blood methylome signatures in children exposed to maternal type 1 diabetes are linked to protection against islet autoimmunity
Exposure to maternal type 1 diabetes (T1D) during pregnancy provides relative protection against T1D in the offspring. This protective effect may be driven by epigenetic mechanisms. Here we conducted an epigenome-wide blood analysis on 790 young children with and 962 children without a T1D-affected mother, and identified differential DNA methylation (q < 0.05) at multiple loci and regions. These included the Homeobox A gene cluster and 15 T1D susceptibility genes. The differential methylation was found in transcriptionally relevant regions associated with immune function, including sites previously linked to T1D-related methylation loci and protein biomarkers. Propensity scores for methylation at T1D susceptibility loci could predict the development of islet autoimmunity in offspring born to mothers without T1D. Together, these findings highlight pathways through which maternal T1D may confer protection against islet autoimmunity in offspring and suggest that environmental factors can influence T1D risk through epigenetic modifications of T1D susceptibility loci.
Authors
- Kristina Casteels (ORCID: https://orcid.org/0000-0001-9690-3551)
- Olga Kordonouri (ORCID: https://orcid.org/0000-0001-9563-3537)
- Christiane Winkler (ORCID: https://orcid.org/0000-0002-7606-3687)
- Ezio E. Bonifacio (ORCID: https://orcid.org/0000-0002-8704-4713)
- Eleftheria Zeggini (ORCID: https://orcid.org/0000-0003-4238-659X)
- Jose Zapardiel‐Gonzalo (ORCID: https://orcid.org/0000-0002-9098-1652)
- Manu Vatish (ORCID: https://orcid.org/0000-0002-6012-2574)
- Peter Kreitmaier (ORCID: https://orcid.org/0000-0001-7431-4529)
- Helena Elding Larsson (ORCID: https://orcid.org/0000-0003-3306-1742)
- Sandra Hummel (ORCID: https://orcid.org/0000-0001-6554-5974)
- Raffael Ott (ORCID: https://orcid.org/0000-0002-5178-1033)
- Agnieszka Szypowska (ORCID: https://orcid.org/0000-0002-3407-3174)
- Annette Knopff
- Angela Hommel (ORCID: https://orcid.org/0009-0002-0054-6436)
- Anette G. Ziegler (ORCID: https://orcid.org/0000-0002-6290-5548)
Institutions
- Lund University (SE)
- Medical University of Warsaw (PL)
- Universitair Ziekenhuis Leuven (BE)
- John Radcliffe Hospital (GB)
- Helmholtz Zentrum München (DE)
- University of Oxford (GB)
- Kinderkrankenhaus auf der Bult (DE)
- Skåne University Hospital (SE)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- Paul Langerhans Institute Dresden (DE)
- Heinrich Heine University Düsseldorf (DE)
- Technical University of Munich (DE)
- Technische Universität Dresden (DE)
- KU Leuven (BE)
Publication Details
- Journal
- Nature Metabolism
- Published
- 2025-11-06
- DOI
- https://doi.org/10.1038/s42255-025-01403-w
- Citations
- 1
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.82