Changes of DNA methylation are associated with changes in lung function during adolescence

Area of Science:

• Epigenetics and Developmental Biology
• Pulmonology and Respiratory Health

Background:

• Adolescence is critical for gender-specific lung function development.
• DNA methylation (DNA-M) influences lung function and changes over time.
• Investigating dynamic DNA-M at specific sites (CpGs) related to lung function is crucial.

Purpose of the Study:

• To examine associations between changes in DNA methylation at lung-function-related CpGs and lung function changes during adolescence.
• To determine the gender-specific nature of these epigenetic associations.
• To identify the biological significance of any detected CpGs.

Main Methods:

• Genome-scale DNA methylation profiling using Illumina arrays (450K and EPIC) on peripheral blood samples from the Isle of Wight birth cohort at ages 10 and 18.
• Spirometry measurements for lung function assessment at both time points.
• Linear regression analyses, stratified by gender, to associate changes in DNA-M with changes in lung function, with validation in ALSPAC and BAMSE cohorts.

Main Results:

• Significant associations were found between DNA-M changes and lung function changes (FEV1/FVC) in females, with 42 CpGs identified.
• No significant CpGs were identified for males.
• Replication in independent cohorts confirmed 11 CpGs consistently associated with lung function changes in females, revealing significant biological pathways.

Conclusions:

• Eleven specific CpGs demonstrate consistent associations with lung function changes during adolescence in females across multiple cohorts.
• These CpGs represent potential candidate epigenetic biomarkers for monitoring lung function development in adolescent females.
• The findings highlight the role of epigenetics in gender-specific lung function trajectories during adolescence.