| Sumario: | Background: The association between attention‐deficit hyperactivity disorder (ADHD) and allergic diseases in children has been reported in observational studies, yet whether the relationship reflects causality remains unclear. Methods: To address this, we performed a two‐sample bidirectional Mendelian randomization (MR) analysis using genetic instrumental variables associated with ADHD (N = 38 691) and childhood allergy (N = 5337) from the largest available genome‐wide association studies. Inverse‐variance weighted was used as the primary estimate, whereas Cochran's Q test and MR‐Egger regression were used to detect heterogeneity and pleiotropy. Results: The main MR estimates indicated that ADHD significantly associated with the risk of allergic diseases in children (odds ratio = 1.14, 95% confidence interval: 1.02–1.27, p = 0.017). The mediation analysis via two‐step MR showed no evidence for mediating roles of gut microbiota and metabolites in the effect of ADHD on childhood allergy. Conclusions: These findings may inform neuroimmune interaction and interventions for allergic diseases in children with ADHD. SUMMARY: ADHD is significantly associated with an increased risk of childhood allergic diseases.This study is the first to use Mendelian randomization to explore the potential causal relationship between ADHD and childhood allergy.No mediating effect of gut microbiota or serum metabolites was found in the causal pathway from ADHD to allergy.The findings support the hypothesis of a direct neuroimmune interaction between the brain and immune system.Early screening for allergic conditions in children with ADHD may improve clinical management and preventive strategies.
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