The association of vitamin D and fibrotic disease: a Mendelian randomization Study

Abstract

Abstract Previous observational studies have suggested a potential link between vitamin D deficiency and an increased risk of fibrotic disease. However, the results may be influenced by various factors, including reverse causation. To investigate the causal relationship between serum vitamin D levels and the risk of fibrotic disease, we performed a Mendelian randomization (MR) analysis. We conducted a comprehensive analysis using genome-wide association study summary statistics for 25-hydroxyvitamin D and five fibrotic diseases: systemic sclerosis, idiopathic pulmonary fibrosis, liver fibrosis and cirrhosis, skin scarring and fibrosis, and primary sclerosing cholangitis. We screened SNPs significantly associated with serum 25-hydroxyvitamin D levels as preliminary instrumental variables excluding SNPs associated with potential confounding factors. We utilized MR-PRESSO to identify potential horizontal pleiotropy effects. After removing outliers, we conducted MR analysis on the remaining SNPs. Furthermore, a series of sensitivity analyses were conducted to ensure the robustness and reliability of the results. This study reveals that there is no established causal relationship between genetically predicted vitamin D concentration and the risk of fibrotic diseases. Consequently, the role of vitamin D as a potential intervention and monitoring tool for fibrotic diseases may not have practical clinical significance.