An inverse causal relationship between serum 25-hydroxyvitamin D levels and pulmonary hypertension: A two-sample Mendelian randomization study

Abstract

Observational studies have confirmed that 25-hydroxyvitamin D (25(OH)D) is associated with pulmonary hypertension (PH), but the causal association between each other is unclear. Therefore, Mendelian randomization (MR) method was performed to validate the causal association between PH and serum 25(OH)D levels. The summary data for 25(OH)D and PH were from the National Human Genome Research Institute-European Bioinformatics Institute. Catalog of human genome-wide association studies and FinnGen biobank consortium. MR analysis was utilized to explore the potential causal association between PH and 25(OH)D. To evaluate this association, inverse variance weighting was considered as the primary method. Cochran's Q test, MR-Egger intercept test, and "leave-one-out" sensitivity analyses were utilized to control the pleiotropy and heterogeneity in the study. Two-sample MR analysis revealed an inverse causal relationship between 25(OH)D and PH (odds ratio: 0.376, 95% confidence interval: 0.162-0.876, p = 2.334 × 10^-2). There was no significant heterogeneity and pleiotropy. The present study confirmed the inverse causal relationship between 25(OH)D and PH. This pathway may provide another treatment pathway in PH. Further studies to elucidate this pathway is indicated.

Keywords: Mendelian randomization; genome‐wide association study; pulmonary hypertension; the causal link; vitamin D.