Association of Venous Thromboembolism Risk with Atopic Dermatitis and Janus Kinase Inhibitors Treatment: A Mendelian Randomization Study

Background The risk of venous thromboembolism (VTE) among patients with atopic dermatitis (AD), especially when receiving treatment with Janus kinase inhibitors (JAKi), has been reported in observational studies. however, the causal relationships between them remain unclear. We aim to explore the causal effects of AD and JAKi on VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). Methods Two-sample Mendelian randomization (MR) analyses were conducted to examine the causal between genetic susceptibility to AD or JAKi target genes (including JAK1, JAK2, JAK3 and tyrosine kinase 2 [TYK2]) and VTE (encompassing DVT and PE) using summary statistics from genome-wide association studies and eQTLGen project. Inverse variance weighting with random effect method was used as the main analytic approach. Pleiotropy and heterogeneity tests were conducted to assess the robustness of the findings. Results No significant causal effects were found between AD and the risk of (odds ratio [OR]: 0.97, 95% confidence interval [CI]: 0.91-1.03, P = .352), DVT (OR: 0.99, 95% CI: 0.89-1.10, P = .789), and PE (OR: 1.06, 95% CI: 0.93-1.20, P = .387). Similarly, there was no causal association between the expression of JAK1, JAK2, JAK3 or TYK2 and VTE, DVT and PE. Conclusion The MR analysis revealed no genetic causal relationships between either AD or JAKi target genes and VTE. These findings may provide a reference for clinicians in prescribing JAKi for patients with AD.