Cholesterol and Vitamin D and the Risk of Hyperemesis Gravidarum: A Mendelian Randomization Study

Background: Hyperemesis Gravidarum (HG) is becoming an increasingly substantial societal burden which affects 0.3–10.8% of pregnant women. Observational studies have investigated the impact of cholesterol and vitamin D on HG. However, the causality of associations among vitamin D, cholesterol and HG remains unknown. Methods We employed Bidirectional Mendelian randomization (MR) analysis and Multivariable MR (MVMR) to investigate the causal associations between cholesterol, vitamin D and HG. The causality was mainly evaluated by inverse variance weighted method (IVW), meanwhile sensitivity analysis was performed by Cochrane Q test, MR-Egger intercept test, Funnel plot and Leave-one-out method. Bonferroni correction was used to determine causal association characteristics. Estimates from two different vitamin D sources were combined using the Fixed-effects meta-analysis methods. Results Our Two-sample MR results identified the effect of genetically predicted decreased vitamin D levels on increased genetic susceptibility to HG ( p  = 0.0006, OR 0.63, 95%CI 0.49–0.82). Our results also indicating that genetically predicted hypercholesterolemia contributes to increased genetic susceptibility to HG ( p  = 0.014; OR 1.24, 95%CI 1.04–1.48). However, in the MVMR analysis with hypercholesterolemia and vitamin D as co-variables, the causal relationship between hypercholesterolemia and HG was no longer significant ( p  = 0.479, OR 1.09, 95% CI 0.87–1.36), and the causal relationship between vitamin D and HG did not show significant changes ( p  = 0.012, OR 0.60, 95% CI 0.40–0.89). Sensitivity analyses were used to confirm the reliability. Conclusion This study provided evidence of a causal relationship between vitamin D and HG. Appropriate vitamin D supplementation have the potential to serve as a preventive and treatment measure for HG.