Background:  The association between newborn DNA methylation (DNAm) and asthma acquisition (AA) during adolescence has been suggested. Lung function (LF) is a predictor of asthma risk and severity. However, it is unclear whether the newborn epigenetic features are consistent between AA during adolescence and preadolescence LF.

Objectives: This study aimed to assess newborn epigenetic features of preadolescence LF and AA during adolescence, along with their biological pathways and processes.

Methods: The study was based on data from the Isle of Wight Birth cohort (IOWBC). Subjects with DNAm at birth and asthma-free at age 10 were included (females, n=249; males, n=187). The R package ttScreening was applied to identify CpGs potentially associated with AA from 10 to 18 years and with LF at age 10 (FEV1, FVC, and FEV1/FVC), respectively. The overlapped CpGs between AA and LF are examined, along with their biological pathways and processes via the R function gometh.

Results: In total, 292 CpGs were detected for AA and 1966 unique CpGs for LF (729 for FEV1, 1243 for FVC, and 600 for FEV1/FVC), with two overlapping CpGs, cg06414095 (MUM1) and cg04407253 (DENND1A). Enrichment analyses indicated non-specific connections in the biological pathways and processes between AA and LF.

Conclusions: The present study suggests that FEV1, FVC, FEV1/FVC (as objective measures of LF), and AA (as a disease outcome) may have their own specific epigenetic features and biological pathways at birth. Replication in a different cohort is desirable to confirm whether the above findings are reproducible.