DNA methylation at birth is associated with lung function development until age 26 years.

Area of Science:

• Epigenetics
• Pulmonology
• Developmental Biology

Background:

• Little is known about the relationship between DNA methylation (DNAm) at birth and lung function development.
• DNAm patterns may influence lung function trajectories throughout life.

Purpose of the Study:

• To investigate whether DNA methylation (DNAm) at birth predicts lung function development.
• To identify specific CpG sites associated with lung function trajectories in children.
• To explore the potential of these DNAm patterns as targets for preventative interventions.

Main Methods:

• Epigenome-wide screening of DNAm from heel prick blood in the Isle of Wight birth cohort (IOWBC-F1).
• Replication of findings using cord blood DNAm in the Avon Longitudinal Study of Parents and Children (ALSPAC).
• Analysis of lung function trajectories over 26 years, stratified by sex, and investigation of associations with gene expression.

Main Results:

• Differential DNAm of eight CpGs on genes GLUL, MYCN, HLX, LHX1, COBL, COL18A1, STRA6, and WNT11 were significantly associated with lung function in both cohorts.
• These associations were consistent in direction and showed stable patterns over time.
• CpGs on LHX1 and COL18A1 were linked to gene expression in a subsequent generation.

Conclusions:

• Novel DNA methylation patterns at birth are associated with lung function trajectories in adolescence and early adulthood.
• These findings provide potential targets for preventative interventions to improve pulmonary function development.
• This study highlights the role of epigenetics in early lung development.