Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course

Area of Science:

• Epigenetics
• Pulmonology
• Genetics

Background:

• Childhood lung function, asthma, and chronic obstructive pulmonary disease (COPD) have complex etiologies.
• Epigenetic modifications, such as DNA methylation, may play a role in respiratory health and disease.
• Cord blood DNA methylation is a potential biomarker for early life exposures and long-term health outcomes.

Purpose of the Study:

• To identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma, and COPD.
• To explore the relationship between identified DMRs and gene expression, biological pathways, and respiratory diseases across the life course.

Main Methods:

• Meta-analysis of epigenome-wide data from 1688 children across five cohorts.
• Identification of cord blood DMRs associated with lung function parameters (FEV1, FEV1/FVC, FEF75) at ages 7-13 years.
• Exploration of DMR associations with childhood asthma, adult lung function, COPD, gene expression, and biological pathways.

Main Results:

• 59 DMRs were associated with childhood lung function, with 18 linked to childhood asthma and nine to adult COPD.
• Top DMR-associated genes include HOXA5, PAOX, ABCA7, CLCA1, and TCL1A.
• Differential gene expression was observed for 32 DMRs in childhood and 18 in adulthood, with 16 DMRs linked to respiratory development or disease pathways.

Conclusions:

• Epigenetic patterns in newborn cord blood are associated with respiratory health and disease throughout life.
• These findings underscore the importance of early-life epigenetics in determining long-term respiratory outcomes.
• The identified DMRs and associated genes provide potential targets for understanding and preventing respiratory diseases.