Exploring causal link of 25-hydroxyvitamin D with eating disorder risk via bidirectional Mendelian randomization.

Eating disorders (EDs) are severe psychiatric diseases characterized by disordered dietary behavior and malnutrition. Previous observational studies found an ambiguous correlation between low levels of serum 25-hydroxyvitamin D (25OHD) and EDs, and the causality remains unclear. This study aims to investigate the causality between 25OHD and EDs with a 2-sample bidirectional Mendelian randomization (MR) analysis. A large database of genome-wide association studies was the source of the single-nucleotide polymorphisms employed in our study. The primary approach to evaluate the causal links between 25OHD and EDs was the fixed-effects inverse-variance weighted (IVW) model. The complementary MR approaches included MR-Egger, weighted median, weighted-mode, and MR Robust Adjusted Profile Score (MR-RAPS). False discovery rate (FDR) was applied to correct for multiple testing. In sensitivity analyses, Cochran Q, MR-Egger intercept and MR-PRESSO tests were used to validate the robustness of MR results. Lastly, we conducted multivariable MR (MVMR) to determine the direct causal effects of 25OHD on EDs. The results of forward MR analyses suggested that higher vitamin D intake tended to lower the risk of genetic susceptibility to anorexia nervosa (ORIVW = 0.43, 95% CI = 0.25-0.74, P = .002, PFDR = .009). Whereas, no causal link was identified between 25OHD and bulimia nervosa (ORIVW = 0.84, 95% CI = 0.25-2.82, P = .780, PFDR = .844). Similar results were found in replication datasets and MVMR analyses. The reverse MR analysis revealed no causal connections. No intergenic heterogeneity and no horizontal pleiotropy were detected. Our findings reminded us that daily vitamin D supplementation may be beneficial in preventing anorexia nervosa and the effect of 25OHD on bulimia nervosa needs to be further studied.