Bidirectional causal association and shared anti-inflammatory target of asthma and atopic dermatitis: a Mendelian randomization and colocalisation study

To investigate the causal relationship between asthma and atopic dermatitis (AD), and to identify potential therapeutic targets for their co-treatment. All summary statistics were sourced from publicly available genome‑wide association studies. Two‑sample Mendelian randomization (MR) analysis was employed to assess the causal relationship between asthma and AD, as well as the causal effects of 91 circulating inflammatory proteins on both conditions. Rigorous sensitivity analyses were conducted to verify the robustness of the findings. Colocalisation analysis was employed to determine whether the exposure and outcome were driven by shared single nucleotide polymorphisms. Additionally, molecular docking was used to validate the interactions of natural active ingredients with interleukin-6 (IL-6). In the discovery cohorts, the MR results revealed an estimated effect of asthma on AD (OR = 1.224, 95% CI = 1.172–1.278, P = 5.89e-20) and an estimated effect of AD on asthma (OR = 1.229, 95% CI = 1.167–1.294, P = 4.83e-15). The MR analysis of replication cohorts yielded consistent results. IL-6 was identified being associated with both asthma and AD. Colocalisation analysis revealed that a shared causal variant within the selected gene locus was significantly associated with IL-6 and AD. However, no evidence was found to support the association of the shared variant with AD and asthma, or with IL-6 and asthma. Four natural active ingredients that interact with IL-6 were identified through molecular docking. IL-6 and atractylenolide I exhibited the lowest binding energy (-7.50 kcal/mol). Our study demonstrated a bidirectional genetic correlation between asthma and AD. IL-6 may represent a therapeutic target for the concurrent management of both conditions.