Exploring the causal relationship between 25-hydroxyvitamin D and asthma: A bidirectional Mendelian randomization study

The role of 25-hydroxyvitamin D (25(OH)D) in disease has attracted much attention. However current research findings on the relationship between 25(OH)D and asthma are not completely consistent. This study aims to explore the potential causal relationship between 25(OH)D levels and asthma using a bidirectional Mendelian randomization (MR) approach. Data from large genome-wide association studies related to the study phenotypes were utilized. Genetic correlation data for 25(OH)D were obtained from the European Bioinformatics Institute database, and genetic correlation data for asthma risk were sourced from the FinnGen biobank. A 2-sample MR analysis was conducted, primarily using the inverse-variance weighted method to assess the impact of 25(OH)D levels on asthma. Sensitivity analyses and horizontal pleiotropy tests were performed to ensure the reliability of the results. Additionally, a reverse MR analysis was conducted to explore potential reverse causal relationships. The MR analysis indicated no significant causal relationship between 25(OH)D levels and allergic asthma (odds ratio [OR] = 1.13, 95% CI: 0.91–1.40, P = .259) or nonallergic asthma (OR = 1.06, 95% CI: 0.89–1.28, P = .501). Furthermore, the reverse MR analysis did not reveal a significant impact of asthma on 25(OH)D levels (allergic asthma: OR = 1.01, 95% CI: 0.99–1.02, P = .363; nonallergic asthma: OR = 1.03, 95% CI: 0.98–1.07, P = .235). The consistency of results across sensitivity analyses and various statistical methods supports this conclusion. Evidence from bidirectional MR suggests no causal relationship between 25(OH)D levels and either allergic or nonallergic asthma.