Causal association of allergic diseases, eosinophils, and osteoporosis: A Mendelian randomization study

The association between allergic diseases and osteoporosis remains controversial. We hypothesize that this discrepancy may be due to a mediator that plays a role in the pathogenesis of both allergic diseases and osteoporosis. To test this hypothesis, we used Mendelian randomization (MR) analysis to investigate the relationships among allergic diseases, eosinophils, and osteoporosis.

This study utilized data from publicly available GWAS databases, including 3 allergic diseases: asthma, allergic rhinitis, and eczema. We conducted bidirectional MR analyses on the relationships between allergic diseases and eosinophils (including eosinophil counts and percentage), allergic diseases and osteoporosis, and eosinophils and osteoporosis, respectively. We conducted sensitivity analyses for results with significance, validated the findings using multivariable Mendelian randomization (MVMR) analysis to ensure the reliability of the significant results.

Two-sample MR analysis revealed significant bidirectional causal relationships between the 3 allergic diseases and eosinophils. A unidirectional causal relationship was found between eosinophils and osteoporosis, with eosinophil counts associated with osteoporosis (OR: 1.194; 95% CI 1.064 to 1.339; Pivw <0.001) and eosinophil percentage associated with osteoporosis (OR: 1.187; 95% CI 1.057 to 1.332; Pivw <0.001). Sensitivity analyses indicated no pleiotropy, However, the association between eosinophil percentage and osteoporosis was no longer significant after multivariable (MVMR) analysis. Additionally, no causal effects were observed from allergic diseases to osteoporosis, from osteoporosis to allergic diseases, or from osteoporosis to eosinophils.

1.) There is a significant bidirectional potential causal relationship between the 3 allergic diseases (asthma, allergic rhinitis, eczema) and eosinophils. 2.) There is no evidence to support a causal relationship between the 3 allergic diseases and osteoporosis, and vice versa. 3.) There is a unidirectional causal relationship may exist from eosinophil counts to osteoporosis.