Leskien Miriam, Thiering Elisabeth, Yu Zhebin, Huels Anke, Yao Yueli, Merid Simon Kebede, Gruzieva Olena, Weidinger Stephan, Waldenberger Melanie, Peters Annette, Melén Erik, Standl Marie
Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Medical Faculty, Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany.
Allergy. 2025 Jul;80(7):1912-1922. doi: 10.1111/all.16583. Epub 2025 May 10.
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.
很少有研究使用主要针对成年人训练的传统时钟来显示儿童过敏性疾病与表观遗传衰老之间的关联。追踪生命早期的DNA甲基化变化表明这些时钟在儿童中的表现不佳。因此，我们旨在使用儿科时钟来阐明过敏性疾病与表观遗传年龄之间的关联。
我们使用了来自德国LISA出生队列研究的数据，分别在6岁（N = 234）和10岁（N = 227）时进行。使用Infinium甲基化EPIC芯片在血液中测量DNA甲基化。我们使用Wu等人（《衰老》，2019年）开发的儿科时钟计算表观遗传年龄（中位绝对误差 = 0.04岁，与实际年龄的Spearman相关性r = 0.75）。使用线性混合模型来检验表观遗传年龄加速与医生诊断的哮喘、鼻炎和湿疹或其组合（“任何过敏”）以及空气过敏原致敏之间的纵向关联。在BAMSE研究的8年随访中（N = 625）使用线性模型进行复制。此外，使用Horvath时钟估计KORA F4研究中成年人的表观遗传年龄，并应用线性模型测试与过敏性疾病的关联。
在LISA研究中，使用Wu的时钟，患有任何过敏与平均表观遗传年龄加速0.34岁显著相关（95%可信区间 = [0.06; 0.63]）。在过敏性鼻炎、哮喘和湿疹中发现了具有一致效应方向的关联。未观察到与空气过敏原致敏的关联。在BAMSE研究中，发现表观遗传年龄加速与湿疹呈负相关（-0.52岁，95%可信区间 = [-0.97; -0.07]）。在KORA研究中，使用Horvath全组织时钟时，花粉热与表观遗传年龄加速显著相关（1.05岁，95%可信区间 = [0.21; 1.89]）。
我们发现来自LISA研究的患有过敏性疾病的儿童表观遗传年龄增加。我们的结果表明，表观遗传年龄加速似乎与过敏性疾病的持续负担有关，但与无症状的空气过敏原致敏无关。
