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Zeller, I. ; Weiss, A. ; Hummel, S. ; Ziegler, A.-G. ; Bonifacio, E.

Age-dependent gene expression trajectories during early childhood in children at increased risk for type 1 diabetes.

Genes Immun., DOI: 10.1038/s41435-025-00324-8 (2025)
DOI PMC
Early childhood is a period of rapid growth and immune system development. It is also critical for type 1 diabetes (T1D) autoimmunity, which has a peak incidence between 1 and 2 years of age. Here, we investigated age-related longitudinal gene expression changes in peripheral blood mononuclear cells from children aged 3 months to 3 years who had an increased genetic risk for T1D, aiming to delineate gene expression trajectories and identify patterns potentially linked to the development of islet autoimmunity. We found 2 432 genes (12.5% of analyzed genes) to exhibit significant temporal dynamics in the first 3 years of life. These genes were grouped into six major clusters each demonstrating distinct expression trajectories of consistent increase or decrease with age, as well as U-shaped, and inverted U-shaped age-related patterns. Notably, genes in clusters with U-shaped expression trajectories, which mirrored the incidence of islet autoantibodies, were enriched for T1D susceptibility genes, particularly within the Major Histocompatibility Complex (MHC) region. This study underscores the dynamic nature of gene expression in early childhood and its potential connection to T1D risk.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Susceptibility
ISSN (print) / ISBN 1466-4879
e-ISSN 1476-5470
Zeitschrift Genes and Immunity
Verlag Nature Publishing Group
Verlagsort Campus, 4 Crinan St, London, N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pancreatic Islet Research (IPI)
Institute of Diabetes Research (IDF)
Förderungen Deutsche Forschungsgemeinschaft
EASD-Novo Nordisk Foundation Diabetes Prize for Excellence
Novo Nordisk Fonden (Novo Nordisk Foundation)