ObjectiveThe inconsistency in conclusions from early observational studies has sparked our interest in elucidating the relationship between lipid levels and susceptibility to hyperemesis gravidarum (HG). This study wishes to employed Mendelian randomization analysis to investigate the causal relationship between low-density lipoprotein cholesterol (LDL-C) and HG.MethodsWe employed Tow-Sample MR analysis to investigate the causal associations between LDL-C and HG. Specific variables were selected from GWAS database for MR analysis, using single nucleotide polymorphisms (SNPs) as our instruments. The threshold for significant SNPs as genetic instruments has been set at 5 x 10-8. F-statistic was employed to validate the strength of exposure instruments. The causality was mainly evaluated by Inverse Variance Weighted method (IVW). To address potential bias from the selection of genetic variants with pleiotropic effects, sensitivity analysis was performed by Cochrane Q-test, MR Egger, weighted median, MR-PRESSO and Leave-one-out methods. To validate the directionality of causal relationships, we employed Steiger test to filter SNPs. At last, we conducted reverse MR to exclude the causal impact of HG on LDL-C levels.ResultsOur MR results identified the effect of genetically predicted increased LDL-C levels on increased genetic susceptibility to HG (OR:1.30; 95%CI:1.03-1.65; p = 0.028). In reverse MR analyses, no evidence was found for causal effect of HG on LDL-C levels (OR:1.00; 95%CI:1.00-1.01; p = 0.163). Sensitivity analyses were used to confirm reliability.ConclusionThis study may have provided evidence of genetically predicted increased LDL-C levels on increased genetic susceptibility to HG. Appropriate lowering LDL-C levels may serve as a preventive and treatment measure for HG.