Is Vitamin D Deficiency the Cause or the Effect of Systemic Lupus Erythematosus: Evidence from Bidirectional Mendelian Randomization Analysis

BACKGROUND: Vitamin D deficiency is common in patients with systemic lupus erythematosus (SLE). Observational studies have reported that it is associated with SLE. In this bidirectional Mendelian randomization (MR) study, we explored the genetic association between serum vitamin D (VD) levels and SLE using two models. METHODS: Genetic variants associated with vitamin D (n = 304,181), 25-hydroxyvitamin D levels (n = 401,460), and SLE (n = 213,683) at genome-wide significance (P < 5∗10(−8)) derived from large-scale publicly available GWAS data were used as instrumental variables. Bidirectional two-sample MR analyses were performed using the inverse variance weighted method (IVW, random, or fixed effect model). Sensitivity analyses including maximum likelihood, MR-Egger method, penalized weighted median method, MR-PRESSO, MR-RAPS, and MR-radial method were conducted. RESULTS: The findings showed that genetically predicted SLE using the IVW method had a negative effect on the vitamin D and 25-hydroxyvitamin D levels in the two models. The results of sensitivity analyses of different analytical approaches were consistent. CONCLUSIONS: These findings indicated that genetically determined SLE had a negative effect on the vitamin D and 25-hydroxyvitamin D levels. Future studies, including random controlled clinical trials, should evaluate the association and mechanisms between serum VD levels and SLE.