Using a Two-Sample Mendelian Randomization Study Based on Genome-Wide Association Studies to Assess and Demonstrate the Causal Effects of Allergic Rhinitis on Chronic Lower Respiratory Diseases and Lung Function

Abstract

Introduction: Observational studies have reported that allergic rhinitis (AR) was associated with chronic lower respiratory diseases (CLRDs) and lung function; however, their causal effects remain elusive. Therefore, to investigate the causal effects of AR on CLRDs and lung function, we conducted the two-sample Mendelian randomization (MR) study.

Methods: The data for AR, asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, idiopathic pulmonary fibrosis (IPF), and the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio were obtained from genome-wide association studies, which were large sample studies on people of European ancestry. In this study, single-nucleotide polymorphisms associated with AR were considered instrumental variables. We employed the inverse-variance weighted (IVW) method with random effects to evaluate causal effects, and the weighted median and MR-Egger methods were used for sensitivity analyses. Significant causal associations were attempted for replication and meta-analysis.

Results: In the discovery stage, we found that AR exhibited a significant causal effect on asthma (IVW, odds ratio [OR] = 16.91, 95% CI, 8.03-35.65, p < 0.001) and a suggestive effect on FEV1/FVC ratio (IVW, OR = 0.82, 95% CI, 0.68-0.99, p = 0.039). No causal effect of AR was observed on COPD, bronchiectasis, and IPF. In the replication stage, the causal effect of AR on asthma was replicated (IVW, OR = 11.57, 95% CI, 4.90-27.37, p < 0.001). The meta-analysis demonstrated that the combined OR of AR on asthma was 14.37 (IVW, 95% CI, 8.18-25.24, p < 0.001).

Conclusions: We demonstrated and measured the causal effects of AR on asthma (OR = 14.37) and FEV1/FVC ratio (OR = 0.82), while there was no evidence to support a causal effect of AR on COPD, bronchiectasis, and IPF. These results suggest that AR tends to have a causal effect on lower airway disease of similar inflammatory types and can provide high-quality causal evidence for clinical practice as well as the pathogenesis and prevention of AR and asthma.

Keywords: Allergic rhinitis; Causal effect; Chronic lower respiratory diseases; Lung function; Mendelian randomization.