背景:哮喘与上呼吸道疾病和过敏性疾病相关;然而,因果关系需要进一步研究。因此,我们进行了两个样本孟德尔随机(MR)分析,以探索和测量哮喘对过敏性鼻炎(AR)的因果关系,血管运动性鼻炎(VMR),过敏性结膜炎(AC),特应性皮炎(AD),过敏性荨麻疹(AU)。
方法:哮喘的数据,AR,VMR,AC,AD,和AU是从最近总结的大规模全基因组关联研究中获得的。我们将满足MR假设的单核苷酸多态性定义为工具变量。随机效应下的逆方差加权(IVW)方法被用作因果估计的主导方法。加权中位数法,MR-Egger回归分析,MR多效性残差和异常值测试,和留一法敏感性分析作为敏感性分析.使用MR-Egger回归分析测量水平多效性。对复制和荟萃分析尝试了显著的因果效应。
结果:我们发现哮喘对AR有因果关系(IVW,优势比[OR]=1.93;95%置信区间[CI],1.74-2.14;p<0.001),VMR(IVW,OR=1.40;95%CI,1.15-1.71;p<0.001),交流(IVW,OR=1.65;95%CI,1.49-1.82;p<0.001),和AD(IVW,OR=2.13;95%CI,1.82-2.49;p<0.001)。未观察到哮喘对AU的因果效应。灵敏度分析进一步确保了这些结果的鲁棒性。复制阶段的评估和荟萃分析进一步证实了哮喘对AR的因果关系(IVWOR=1.81,95%CI1.62-2.02,p<0.001),AC(IVWOR=1.44,95%CI1.11-1.87,p<0.001),和AD(IVWOR=1.85,95%CI1.42-2.41,p<0.001)。
结论:我们揭示并量化了哮喘对AR的因果影响,VMR,AC,和AD。这些发现可以为哮喘对上呼吸道疾病和过敏性疾病的影响提供有力的因果证据,表明哮喘的治疗应该是AR的预防和治疗策略,VMR,AC,和AD。
BACKGROUND: Asthma is associated with upper airway diseases and allergic diseases; however, the causal effects need to be investigated further. Thus, we performed this two-sample Mendelian randomization (MR) analysis to explore and measure the causal effects of asthma on allergic rhinitis (AR), vasomotor rhinitis (VMR), allergic conjunctivitis (AC), atopic dermatitis (AD), and allergic urticaria (AU).
METHODS: The data for asthma, AR, VMR, AC, AD, and AU were obtained from large-scale genome-wide association studies summarized recently. We defined single-nucleotide polymorphisms satisfying the MR assumptions as instrumental variables. Inverse-variance weighted (IVW) approach under random-effects was applied as the dominant method for causal estimation. The weighted median approach, MR-Egger regression analysis, MR pleiotropy residual sum and outlier test, and leave-one-out sensitivity analysis were performed as sensitivity analysis. Horizontal pleiotropy was measured using MR-Egger regression analysis. Significant causal effects were attempted for replication and meta-analysis.
RESULTS: We revealed that asthma had causal effects on AR (IVW, odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.74-2.14; p < 0.001), VMR (IVW, OR = 1.40; 95% CI, 1.15-1.71; p < 0.001), AC (IVW, OR = 1.65; 95% CI, 1.49-1.82; p < 0.001), and AD (IVW, OR = 2.13; 95% CI, 1.82-2.49; p < 0.001). No causal effect of asthma on AU was observed. Sensitivity analysis further assured the robustness of these results. The evaluation of the replication stage and meta-analysis further confirmed the causal effect of asthma on AR (IVW OR = 1.81, 95% CI 1.62-2.02, p < 0.001), AC (IVW OR = 1.44, 95% CI 1.11-1.87, p < 0.001), and AD (IVW OR = 1.85, 95% CI 1.42-2.41, p < 0.001).
CONCLUSIONS: We revealed and quantified the causal effects of asthma on AR, VMR, AC, and AD. These findings can provide powerful causal evidence of asthma on upper airway diseases and allergic diseases, suggesting that the treatment of asthma should be a preventive and therapeutic strategy for AR, VMR, AC, and AD.