The causality between vitamin D and hyperemesis gravidarum remains unknown. Our aim was to investigate the causal effect of vitamin D on hyperemesis gravidarum using the two-sample Mendelian randomization method.

Independent single nucleotide polymorphisms significantly associated with serum 25-hydroxyvitamin D levels served as instrumental variables. The corresponding effect estimates for hyperemesis gravidarum were obtained from the Finngen Biobank. For Mendelian randomization analysis, inverse variance weighting was used as the primary method. We also used weighted median, MR-Egger regression, simple mode, and weighted mode as complementary methods to inverse variance weighting. The MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis were performed to assess the horizontal pleiotropy, heterogeneity, and stability of the causal association between 25-hydroxyvitamin D levels and hyperemesis gravidarum.

We found that an increase in 25-hydroxyvitamin D level was associated with a lower risk of hyperemesis gravidarum [odds ratio (OR): 0.568, 95 % CI: 0.403–0.800, p = 0.001]. The result demonstrates the causal relationship between 25-hydroxyvitamin D level and the risk of hyperemesis gravidarum in the European population.

The large Mendelian randomization analysis suggests that vitamin D may be causally associated with risk of hyperemesis gravidarum.