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

Ivo Zeller1, Andreas Weiss1, Sandra Hummel1

  • 1Institute of Diabetes Research, Helmholtz Munich, German Center for Environmental Health, Munich, Germany.

Genes and Immunity
|March 21, 2025
PubMed

Insights

Gene expression changes rapidly in early childhood, particularly in children at high risk for type 1 diabetes (T1D). Specific age-related patterns, especially U-shaped trajectories, correlate with T1D autoimmunity development.

Area of Science:

  • Immunology
  • Genetics
  • Pediatrics

Background:

  • Early childhood is crucial for immune system development and type 1 diabetes (T1D) autoimmunity onset.
  • T1D autoimmunity incidence peaks between 1 and 2 years of age.
  • Genetic predisposition plays a significant role in T1D development.

Purpose of the Study:

  • To investigate age-related gene expression changes in children at high genetic risk for T1D.
  • To identify gene expression trajectories linked to the development of islet autoimmunity.
  • To understand the dynamic interplay between gene expression and T1D risk in early life.

Main Methods:

  • Analysis of longitudinal gene expression in peripheral blood mononuclear cells from children aged 3 months to 3 years.
  • Identification of genes with significant temporal expression dynamics.
  • Clustering of genes based on distinct age-related expression patterns (increasing, decreasing, U-shaped, inverted U-shaped).

Main Results:

  • Over 2,400 genes (12.5%) showed significant age-related expression changes in the first three years of life.
  • Six distinct gene expression clusters were identified, displaying various temporal dynamics.
  • Genes with U-shaped expression trajectories, mirroring islet autoantibody incidence, were enriched for T1D susceptibility genes, especially in the MHC region.

Conclusions:

  • Gene expression is highly dynamic during early childhood.
  • Specific age-related gene expression patterns, particularly U-shaped trajectories, are associated with T1D autoimmunity.
  • These findings highlight the potential of early life gene expression dynamics in understanding and predicting T1D risk.

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