The causal relationship between allergic diseases and heart failure: Evidence from Mendelian randomization study

Emerging evidence shows allergic diseases, such as atopic dermatitis and asthma, are risk factors of heart failure. However, the causal relationship between allergic diseases and heart failure is not clear.We performed a two-sample Mendelian randomization analysis between allergic diseases and heart failure using summary statistics of genome-wide association studies from large GWAS consortia, with total sample size of 1.2 million. Independent instrumental variables for asthma and atopic dermatitis (P<1×10-5) were used as the exposure. We applied five models for the Mendelian randomization analysis. Finally, we performed the sensitivity analyses to assess the robustness of the results.We have identified 55 independent single nucleotide polymorphisms (SNPs) for asthma 54 independent SNPs for atopic dermatitis as our instrumental variables. The inverse variance-weighted (IVW) analysis showed asthma was significantly associated with increased risk of heart failure (ORIVW = 1.04, 95% CI, 1.01-1.07, P = 0.03). The Mendelian randomization analysis using the other four models also showed consistent results with the IVW analysis. Similarly, atopic dermatitis was also significantly associated with an increased risk of heart failure (ORIVW = 1.03, 95% CI, 1.01-1.06, P = 0.01), consistent with the other four models. The sensitivity analysis showed no evidence of horizontal pleiotropy or results were driven by single SNPs.Our study identified asthma and atopic dermatitis as a causal risk factor for heart failure and suggest inflammatory pathogenesis as a key factor contributing to the underlying mechanism. These findings emphasize the importance of asthma and allergy control in the prevention and management of heart failure.