过敏性鼻炎与静脉血栓的因果关联：两样本双向孟德尔随机化研究

Causal Association between Allergic Rhinitis and Venous Thromboembolism: A Two-Sample Bidirectional Mendelian Randomization Study

摘要: 目的：采用两样本双向孟德尔随机化(MR)分析探讨过敏性鼻炎(AR)与静脉血栓栓塞症(VTE)之间的因果关联。方法：基于大规模全基因组关联研究(GWAS)的汇总数据，筛选与AR及VTE显著相关且相互独立的单核苷酸多态性(SNP)作为工具变量。以逆方差加权固定效应模型(IVW-FE)作为主要分析方法，最大似然法、加权中位数法和MR-Egger回归进行稳定性检验；通过Cochran’s Q检验、MR-Egger截距法、MR-PRESSO及留一法进行敏感性分析。效应值以OR值及其95% CI表示。结果：正向MR分析未发现AR对VTE存在因果关联(P > 0.05)。反向MR分析显示，基因预测的VTE每升高一个标准差，AR的发生风险增加1% (OR = 1.010, 95% CI: 1.004~1.017, P = 0.002)。结论：VTE可能会增加AR的发病风险，这一结果尚需更多研究进一步验证。

Abstract: Objective: To investigate the causal relationship between allergic rhinitis (AR) and venous thromboembolism (VTE) using a two-sample bidirectional Mendelian randomization (MR) approach. Methods: Summary statistics were obtained from large-scale genome-wide association studies (GWAS). Independent single nucleotide polymorphisms (SNPs) significantly associated with AR or VTE were selected as instrumental variables. The inverse variance weighted fixed-effects (IVW-FE) model served as the primary method, with maximum likelihood, weighted median, and MR-Egger regression employed for robustness checks. Sensitivity analyses were conducted using Cochran’s Q test, MR-Egger intercept, MR-PRESSO, and leave-one-out analysis. Effect estimates were reported as odds ratios (OR) with 95% confidence intervals (CI). Results: Forward MR analysis revealed no evidence of a causal effect of AR on VTE (P > 0.05). In contrast, reverse MR analysis indicated that genetically predicted VTE was associated with a 1% increased risk of AR per standard deviation increment (OR = 1.010, 95% CI: 1.004~1.017, P = 0.002). Conclusion: These findings suggest that VTE may increase the risk of AR, although further studies are warranted to validate this causal association.