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Blood methylome signatures in children exposed to maternal type 1 diabetes are linked to protection against islet autoimmunity

Ott, Raffael ; Zapardiel-Gonzalo, Jose ; Kreitmaier, Peter ; Casteels, Kristina ; Hommel, Angela ; Kordonouri, Olga ; Elding Larsson, Helena LU orcid ; Szypowska, Agnieszka ; Vatish, Manu and Zeggini, Eleftheria , et al. (2025) In Nature Metabolism 7(11). p.2236-2249
Abstract

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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Metabolism
volume
7
issue
11
pages
14 pages
publisher
Springer Nature
external identifiers
  • pmid:41198985
  • scopus:105021100884
ISSN
2522-5812
DOI
10.1038/s42255-025-01403-w
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2025.
id
81562106-0d19-4b33-aab5-ea6e613d9184
date added to LUP
2026-01-12 13:15:59
date last changed
2026-01-26 15:10:48
@article{81562106-0d19-4b33-aab5-ea6e613d9184,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Ott, Raffael and Zapardiel-Gonzalo, Jose and Kreitmaier, Peter and Casteels, Kristina and Hommel, Angela and Kordonouri, Olga and Elding Larsson, Helena and Szypowska, Agnieszka and Vatish, Manu and Zeggini, Eleftheria and Knopff, Annette and Winkler, Christiane and Ziegler, Anette G. and Bonifacio, Ezio and Hummel, Sandra}},
  issn         = {{2522-5812}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{2236--2249}},
  publisher    = {{Springer Nature}},
  series       = {{Nature Metabolism}},
  title        = {{Blood methylome signatures in children exposed to maternal type 1 diabetes are linked to protection against islet autoimmunity}},
  url          = {{http://dx.doi.org/10.1038/s42255-025-01403-w}},
  doi          = {{10.1038/s42255-025-01403-w}},
  volume       = {{7}},
  year         = {{2025}},
}