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.

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.