Study discovers links between DNA methylation and gene expression in children

A new study headed by ISGlobal, an organization financed by “Ia Caixa” Foundation, finds links between DNA methylation patterns and gene expression levels in blood samples from youngsters. Researchers will be able to use the results, which were published in eLife, to better understand the connection between early environmental exposures, epigenetic alterations, and disease.

Even while cells from the same person have the same DNA, they do not express the same genes. Each cell type releases a distinct collection of genes, allowing it to perform a specific role. This is controlled by the epigenome, which is made up of chemical alterations to the genome (such as DNA methylation) that may switch genes on or off. The epigenome not only regulates development but also permits cells to respond to environmental influences.

Many studies (known as epigenome-wide association studies) have recently attempted to relate environmental influences to modified DNA methylation patterns and disease. Most investigations, however, do not allow for the determination of whether or not these methylation sites alter the expression of neighboring genes.

Identifying associations between DNA methylation levels and gene expression might help us better interpret epigenome-wide association studies and understand the biological processes leading to disease.”

Mariona Bustamante, Researcher, Universitat Pompeu Fabra, ISGlobal

The researchers used blood samples from 832 children aged 6–11 years from the Human Early Life Exposome (HELIX) project to look for associations between DNA methylation levels at specific locations of the genome and the expression of nearby genes, known as expression quantitative trait methylation or eQTMs.

Firstly, each sample’s methylation and gene expression levels were examined. Secondly, each gene was linked with the methylation site or sites that were nearest to it. Nearly 40,000 significant connections between methylation levels and gene expression were discovered in the study.

In most cases, the methylation site was proximal to the regulated gene, and methylation and gene expression levels had an inverse relationship in 59% of cases (meaning more methylation - lower gene expression). Only 13.8% of the identified relationships were also discovered in adults.

Carlos Ruiz-Arenas, first author of the study adds, “This was expected, as it is known that DNA methylation and gene expression change with age, however differences in study designs can also explain this.”

Our results provide a catalog of methylation-gene expression associations that could become a powerful tool to help researchers interpret epigenome-wide association studies in children.”

Mariona Bustamante, Researcher, Universitat Pompeu Fabra, ISGlobal