Journal Article

The multi-omics signatures of telomere length in childhood

Nawrot, Tim S., Wright, John, Slama, Remy, Borràs, Eva, Sabidó, Eduard, Chatzi, Leda, Carracedo, Angel, McEachan, Rosemary R. C., Anguita-Ruiz, Augusto, Lepeule, Johanna, Bustamante, Mariona, Alfano, Rossella, Plusquin, Michelle, Keun, Hector, Wang, Congrong, Maitre, Lea, Gonzalez, Juan R., Martens, Dries S., Vrijheid, Martine, Grazuleviciene, Regina, Gutzkow, Kristine B., Escarami, Georgia, Pelegrí-Sisó, Dolors, Vafeiadi, Marina

2025

Overview

Background Telomere length is an important indicator of biological age and a complex multi-factor trait. To date, the telomere interactome for comprehending the high-dimensional biological aspects linked to telomere regulation during childhood remains unexplored. Here we describe the multi-omics signatures associated with childhood telomere length. Methods This study included 1001 children aged 6 to 11 years from the Human Early-life Exposome (HELIX) project. Telomere length was quantified via qPCR in peripheral blood of the children. Blood DNA methylation, gene expression, miRNA expression, plasma proteins and serum and urinary metabolites were measured through microarrays or (semi-) targeted assays. The association between each individual omics feature and telomere length was assessed in omics-wide association analyses. In addition, a literature-guided, sparse supervised integration method was applied to multiple omics, and latent components were extracted as predictors of child telomere length. The association of these latent components with early-life aging risk factors (child lifestyle, body mass index (BMI), exposure to smoking, etc.), were interrogated. Results After multiple-testing correction, only two CpGs (cg23686403 and cg16238918 at PARD6G gene) out of all the omics features were significantly associated with child telomere length. The supervised multi-omics integration approach revealed robust associations between latent components and child BMI, with metabolites and proteins emerging as the primary contributing features. In these latent components, the contributing molecular features were known as involved in metabolism and immune regulation-related pathways. Conclusions Findings of this multi-omics study suggested an intricate interplay between telomere length, metabolism and immune responses, providing valuable insights into the molecular underpinnings of the early-life biological aging.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aging / Analysis / Animal Genetics and Genomics / Biological aging / Biological analysis / Biomedical and Life Sciences / Blood / Body mass index / Body size / Child / Childhood / Children / Children & youth / Chromosomes / CpG Islands / DNA Methylation / DNA microarrays / Early-life / Female / Gene expression / Genomes / Health aspects / Humans / Immune response / Immunoregulation / Life Sciences / Male / Measurement / Metabolites / Methylation / Microarrays / Microbial Genetics and Genomics / MicroRNA / MicroRNAs / MicroRNAs - genetics / miRNA / Multi-omics / Multiomics / NMR / Nuclear magnetic resonance / Peripheral blood / Plant Genetics and Genomics / Plasma / Plasma proteins / Proteins / Proteomics / Risk factors / Santé publique et épidémiologie / Signatures / Socioeconomic factors / Telomere - genetics / Telomere - metabolism / Telomere Homeostasis - genetics / Telomere length / Telomeres / Yeast