No Causal Association Between Serum Vitamin D Levels and Bronchiectasis: A Mendelian Randomization Analysis

Observational studies have reported an association between Vitamin D deficiency and an increased risk of bronchiectasis. This study aims to investigate the causal relationship between Vitamin D levels and bronchiectasis using a 2-sample Mendelian randomization (MR) analysis. Data from 2 genome-wide association studies (GWAS) based on European ancestry were analyzed: serum vitamin D levels (sample size = 441,291 [UK Biobank]) and bronchiectasis (sample size = 187,830 [cases = 1107, controls = 186,723; FinnGen]). Inverse-variance weighted (IVW) analysis was primarily used to assess the causal effect of 25(OH)D levels on bronchiectasis, supplemented by Mendelian randomization Egger regression (MR-Egger), weighted median, simple mode, and weighted mode analyses. Additionally, MR-Egger intercept test and MR-Pleiotropy Residual Sum and Outlier methods were implemented to determine pleiotropy, and Cochran's Q test was conducted for heterogeneity testing. Leave-one-out analysis and Bayesian weighted Mendelian randomization was also used to assess the robustness of the results. The MR analysis suggested no significant causal effects of serum 25(OH)D levels on bronchiectasis using the IVW method (odds ratio = 1.550; 95% confidence interval [CI]: 0.908-2.315; P = .120). These results were consistent across MR-Egger regression, weighted median, simple mode, and weighted mode analyses. No significant heterogeneity, pleiotropy, or bias was detected in instrumental variables. Additionally, no evidence supported the causal effects of bronchiectasis on serum vitamin D levels (β = -0.002, 95% CI: -0.007 to 0.003; P = .463). Our study found no significant causal association between serum 25(OH)D levels and bronchiectasis, in either direction. A larger sample-sized randomized controlled trial (RCT) is needed to further investigate this potential causal relationship.