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

## TL;DR

This study explores how gene expression changes during early childhood in children at higher risk for type 1 diabetes, revealing patterns linked to immune development and disease risk.

## Contribution

The study identifies age-dependent gene expression clusters, including U-shaped patterns linked to T1D susceptibility genes.

## Key findings

- 2,432 genes showed significant temporal expression changes in children aged 3 months to 3 years.
- U-shaped gene expression clusters were enriched for T1D susceptibility genes, especially in the MHC region.
- Gene expression trajectories suggest a dynamic immune system development linked to T1D risk.

## Abstract

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.