Mendelian randomization analysis identifies a genetic casual association between circulating C-reactive protein and intracerebral hemorrhage

Background: The causal effect of C-reactive protein (CRP) on intracerebral hemorrhage (ICH) remains contro-versial. We discussed the causal association of CRP with ICH based on two-sample Mendelian randomization. Methods: The data from two genome-wide association studies (GWAS) of European ancestry was extracted, including circulating CRP levels (204,402 individuals) and ICH (1,687 cases and 201,146 controls). The inverse variance weighted (IVW) method was primary tool to evaluate the causal relationship of circulating CRP levels on ICH risk. MR-Egger regression and MR-PRESSO global test were utilized to identify pleiotropy. Heterogeneity was discussed with Cochran's Q test. The leave-one-out analysis explored the reliability of the results. Results: 54 SNPs were identified as instrumental variables (IVs) for circulating CRP levels, and these IVs had no significant horizontal pleiotropy, heterogeneity, or bias. MR analysis demonstrated a causal relationship between elevated circulating CRP levels and decreased risk of ICH (ORIVW = 0.828, 95% CI 0.692-0.992, P = 0.040). Conclusion: Elevated circulating CRP levels demonstrated a significant potentially protective causal relationship with risk of ICH.