Childhood Asthma and Allergy Are Related to Accelerated Epigenetic Aging

Few studies showed associations of childhood allergic diseases with epigenetic aging using traditional clocks trained mainly on adults. Tracking DNA methylation variation early in life has suggested poor performance of these clocks in children. Therefore, we aim to elucidate the association between allergic diseases and epigenetic age using a pediatric clock.

We used data from the German LISA birth cohort study at six (N = 234) and ten (N = 227) years. DNA methylation was measured in blood using the Infinium Methylation EPIC BeadChip. We calculated epigenetic age using the pediatric clock developed by Wu et al. (Aging 2019) (median absolute error = 0.04 years, Spearman correlation with chronological age r = 0.75). Linear mixed models were used to examine longitudinal associations of epigenetic age acceleration with doctor-diagnosed asthma, rhinitis, and eczema, or a combination thereof ("any allergy") as well as aeroallergen sensitization. Replication was performed in BAMSE at the 8-year follow-up (N = 625) using linear models. Additionally, epigenetic age in adults from KORA F4 was estimated using Horvath's clocks and associations with allergic diseases were tested applying linear models.

Having any allergy was significantly associated with a mean epigenetic age acceleration of 0.34 years (95% CI = [0.06; 0.63]) using Wu's clock in LISA. Associations with consistent effect directions were found for allergic rhinitis, asthma, and eczema. No associations with aeroallergen sensitization were observed. In BAMSE, an inverse association of epigenetic age acceleration with eczema was found (-0.52 years, 95% CI = [-0.97; -0.07]). In KORA, hay fever was significantly associated with accelerated epigenetic age when using the Horvath pan-tissue clock (1.05 years, 95% CI = [0.21; 1.89]).

We found an increase in epigenetic age in children with allergic diseases from LISA. Our results suggest that epigenetic age acceleration seems to be related to the persistent burden of allergic diseases, but not to non-symptomatic aeroallergen sensitization.