Causal Effects of Asthma on Upper Airway Diseases and Allergic Diseases: A Two-Sample Mendelian Randomization

Abstract

Introduction: 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.