Causal effects of endometriosis on serum 25-hydroxyvitamin D: Evidence from Mendelian randomization study

The potential bidirectional causal relationship between endometriosis and serum 25-hydroxyvitamin D has been previously investigated. Nevertheless, the results could be impacted by confounding factors and reverse causality because of the nature of observational research. Mendelian randomization (MR) circumvents the drawbacks of observational studies by providing estimates of unconfounded causal effects. We used bi-directional MR analysis to determine whether serum 25-hydroxyvitamin D had a causal influence on endometriosis and vice versa. Additionally, using heterogeneity and sensitivity analyses, we explored the heterogeneity and pleiotropy of effect estimates. Similarly, we investigated the causal correlation between endometriosis and 25-hydroxyvitamin D through reverse-direction MR. In forward-direction MR, we selected 95 single-nucleotide polymorphisms (SNPs) as instrumental variants (IVs) to examine the potential causal influence between 25-hydroxyvitamin D and endometriosis. And we selected 9 SNPs as IVs for reverse-direction MR analyses to examine whether endometriosis has a causal influence on serum 25-hydroxyvitamin D. We found suggestive evidence that endometriosis contributes to higher serum 25-hydroxyvitamin D (β: 0.010, 95% CI: 0.002-0.02, P = .016). Our data suggest that serum 25-hydroxyvitamin D levels may be a consequence of endometriosis rather than a causal risk factor, and its potential role in the disease process warrants further investigation.