Exploring genetic association of allergic disease with cardiovascular disease: A bidirectional Mendelian randomization study

Abstract Background: In observational and experimental studies, allergic diseases have been reported to be associated with some types of cardiovascular diseases. They share a typical pathophysiological process, including inflammatory and metabolism disorders. However, the direction of the causal association between them remains unclear. This Mendelian randomization (MR) study aims to examine the bidirectional causality between allergic diseases and cardiovascular diseases. Methods:We used publicly available GWAS summary statistics data only, including European participants from UK Biobank or on the IEU Open GWAS database. We identified genetic variants associated with allergic diseases, asthma, or cardiovascular diseases as instrumental variables to investigate the genetically causal association between allergic diseases and asthma and the risk of 12 kinds of cardiovascular diseases. MR was performed using analytical methods including the inverse variance weighted (IVW), MR-Egger and, weighted median. Sensitivity tests were also performed in the MR to assess the validity of the casualty. Results: Genetically predicted allergic diseases was associated with essential hypertension [odds ratio (OR)=0.9987, 95% confidence interval (CI): 0.9976-0.9998, P=0.024], and asthma was associated with atherosclerosis (OR=1.0006, 95% CI: 1.0001-1.0012, P=0.02) in the MR analysis with the IVW method. In the reverse MR analyses, we found that essential hypertension was associated with allergic diseases (OR=8.16E-03, 95% CI: 7.55E-05 - 8,82E-01, P=0.044) and asthma (OR=8.16E-03, 95% CI: 7.55E-05 - 8,82E-01, P=0.044), and stroke was associated with allergic diseases (OR=3.59E-02, 95% CI: 1.34E-03 - 9.62E-01, P=0.047). However, no causal effect has been detected bidirectionally after the Bonferroni correction. Conclusion: The MR study found that patients with AD or asthma might have a decreased risk of essential hypertension and an increased risk of atherosclerosis in European individuals. In reverse analysis, essential hypertension, AD, and asthma are negatively correlated, and stroke may decrease the risk of AD. However, after a Bonferroni correction, our evidence did not suggest a significant causal between them, which means that the evidence is weak. Whether AD exerts effects on CVD needs further investigation.