AIM: We aim to assess association of DNA methylation (DNAm) at birth with total immunoglobulin E (IgE) trajectories from birth to late adolescence and whether such association is ethnicity-specific. METHODS: We examined the association of total IgE trajectories from birth to late adolescence with DNAm at birth in two independent birth cohorts, the Isle of wight birth cohort (IOWBC) in UK ( RESULTS: Two total IgE trajectories, high vs. low, were inferred from each of the two cohorts. Associations of DNAm at 103 CpGs with IgE trajectories in IOWBC and at 476 CpGs in MICS were identified. Between the two cohorts, of the identified CpGs, one was in common, methQTL site cg16711274 (mapped to gene MINAR1), and 17 pathways were common with at least four linked to airway diseases. CONCLUSION: The findings suggest at-birth epigenetics may explain ethnicity differences in total IgE trajectories later in life.