The Role of C-Reactive Protein and Fibrinogen in the Development of Intracerebral Hemorrhage: A Mendelian Randomization Study in European Population

Background: The causal association of C-reactive protein (CRP) and fibrinogen on intracerebral hemorrhage (ICH) remains uncertain. We investigated the causal associations of CRP and fibrinogen with ICH using two-sample Mendelian randomization. Method: We used single-nucleotide polymorphisms associated with CRP and fibrinogen as instrumental variables. The summary data on ICH were obtained from the International Stroke Genetics Consortium (1,545 cases and 1,481 controls). Two-sample Mendelian randomization estimates were performed to assess with inverse-variance weighted and sensitive analyses methods including the weighted median, the penalized weighted median, pleiotropy residual sum and outlier (MR-PRESSO) approaches. MR-Egger regression was used to explore the pleiotropy. Results: The MR analyses indicated that genetically predicted CRP concentration was not associated with ICH, with an odds ratio (OR) of 1.263 (95% CI = 0.935–1.704, p = 0.127). Besides, genetically predicted fibrinogen concentration was not associated with an increased risk of ICH, with an OR of 0.879 (95% CI = 0.060–18.281; p = 0.933). No evidence of pleiotropic bias was detected by MR-Egger. The findings were overall robust in sensitivity analyses. Conclusions: Our findings did not support that CRP and fibrinogen are causally associated with the risk of ICH.