Higher 25-hydroxyvitamin D level is associated with increased risk for Behcet's disease

Background & aim: Previous studies showed a vitamin D deficiency in patients with Behcet's disease, suggesting potential benefits of vitamin D supplementation in the prevention and treatment of Behcet's disease. Interpretation of these studies may be limited by reverse causality or confounding bias. We aim to determine the causal association between serum 25-hydroxyvitamin D [25(OH)D] and the risk of Behcet's disease by Mendelian randomization. Methods: An allele score formed by four variants (rs2282679, rs10741657, rs12785878 and rs6013897) that were associated with serum 25(OH)D level, was examined using data of genome-wide association study (GWAS) on 999 Behcet's disease and 4417 healthy individuals of Chinese ancestry and validated using data of GWAS on 1215 Behcet's disease and 1278 controls of Turkish ancestry. The primary outcome was the risk of Behcet's disease, evaluated by an inverse variance weighted average of the associations with genetically determined 25(OH)D levels. Results: The inverse variance weighted estimate showed that genetically increased 25(OH)D level was associated with a higher risk of Behcet's disease. In the Chinese cohort, the odds ratio for Behcet's disease in one standard deviation increase of natural log-transformed 25(OH)D level was 3.82 (95% CI: 1.27 -11.42). Data from Turkish cohort confirmed the association with Behcet's disease (OR, 95% CI: 4.18, 1.15 -15.12). In overall combination of Chinese and Turkish cohorts, the odds ratio for Behcet's disease per standard deviation increase of natural log-transformed 25(OH)D level was estimated to be 3.96 (95% CI: 1.72-9.13; P 1/4 0.001). No significant evidence of pleiotropy and heterogeneity was detected. Conclusions: On the basis of evidence in 7909 human beings, this study provides the newest indication that a lifelong higher 25(OH)D level is associated with an increased risk of Behcet's disease. Special attention should be paid to the potential harm of long-term or high-dose use of vitamin D supplements in clinical practice. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Automated summary

This study using Mendelian randomization found that genetically increased serum 25-hydroxyvitamin D levels were associated with a higher risk of Behcet's disease, with data from Chinese and Turkish cohorts supporting this conclusion. The contribution to Behcet's disease risk may increase with higher levels of vitamin D.