Epigenetic age acceleration and allergic diseases: a bidirectional two-sample Mendelian randomization study

Objective: The epigenetic clock has been regarded as a highly accurate predictor of capturing the complexity between aging and the epigenome. However, there is limited understanding of the epigenetic clock in allergic diseases. The aim of this study was to explore the causal relationship between epigenetic age acceleration and allergic diseases by conducting a bidirectional two-sample Mendelian randomization (MR) study. Methods: Pleiotropy analysis was conducted using the MR-Egger intercept test and the MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) test. Instrumental variables were constructed using single nucleotide polymorphisms. The statistics for epigenetic age acceleration and allergic diseases were derived from genome-wide association studies (GWAS) of European ancestry. MR analysis was performed using inverse variance weighted, weighted median, and MR-Egger methods. Results: Based on the inverse variance weighted method, the forward MR analysis showed that intrinsic epigenetic age acceleration (IEAA) was associated with an increased risk of allergic asthma (OR = 1.051, 95% CI 1.006 to 1.098, p = 0.025). The reverse MR analysis also indicated a significant causal relationship between allergic asthma and IEAA (OR = 1.410, 95% CI 1.111 to 1.791, p = 0.005). However, there was a lack of evidence supporting a causal relationship between IEAA and allergic conjunctivitis, atopic dermatitis, allergic rhinitis and allergic urticaria (all p > 0.05). Quality control assessments demonstrated that our study results were reliable and robust. Conclusions: This study revealed bidirectional causal relationships between intrinsic epigenetic age acceleration and allergic asthma, highlighting potential prevention strategies.