Causal association between allergic diseases and short stature: a mendelian randomization study revealing the potential mediating role of inflammatory proteins

OBJECTIVE: Although observational studies have proven a correlation between allergic diseases and short stature (SS), the causal relationship remains unestablished. Furthermore, inflammatory proteins are closely linked with both conditions; their potential mediating role has yet to be elucidated. This study aimed to probe into the causal linkage between allergic diseases and SS and the mediating role of inflammatory proteins. METHODS: A two-sample MR analysis was employed to explore the causal links between five allergic diseases (allergic rhinitis, childhood asthma, allergic conjunctivitis, atopic dermatitis (AD), and urticaria) and SS. A two-step MR approach was further used to investigate the mediating role of inflammatory proteins. RESULTS: Among the five allergic diseases, MR analysis only identified a suggestive positive correlation between AD and the risk of SS (OR = 1.720, 95%CI: 1.081-2.735, P = 0.022). A suggestive negative association was also found between AD and the level of the inflammatory protein AXIN1 (OR = 0.922, 95%CI: 0.855-0.995, P = 0.037). Mediation analysis revealed that AXIN1 levels potentially mediated 13.5% of the causal pathway between AD and SS risk. CONCLUSION: A potential positive causal link between AD and SS was revealed, highlighting the potential mediating role of the inflammatory protein AXIN1. These findings provide a scientific basis and a novel potential target for interventions aimed at improving height growth outcomes in patients with allergic diseases.