Causal relationship between statins and hemorrhagic stroke: A drug-target Mendelian randomization analysis

This study assesses the causal relationship between lipid phenotypes mediated by drug targets and hemorrhagic stroke using Mendelian randomization (MR) methods. Single nucleotide polymorphism data associated with statin drugs and hemorrhagic stroke were obtained from the IEU Open GWAS database. The inverse variance weighted method was used as the primary analysis, with the weighted median method and MR-Egger regression method also employed for MR analysis. The β values and 95% confidence intervals were used to assess the causal relationship between statins and hemorrhagic stroke. Sensitivity analyses were performed to verify the reliability of the results. Cochran Q test was used to assess heterogeneity, the MR-Egger intercept method tested for horizontal pleiotropy, and leave-one-out analysis was used to determine whether any single or multiple single nucleotide polymorphisms influenced the results. The low-density lipoprotein cholesterol mediated by the statin drug target, 3-hydroxy-3-methylglutaryl-CoA reductase, showed a significant correlation with intracerebral hemorrhage (β = -0.402, 95% confidence interval: 0.450-0.994, P = .0466). These findings support the protective effect of statins on intracerebral hemorrhage. This result not only enhances the understanding of cholesterol-related genes and hemorrhagic stroke but also reveals potential therapeutic targets for hemorrhagic stroke.