Revealing the causal association among clonal hematopoiesis (CH), stroke and circulating inflammatory factors: A Mendelian randomization study

Previous prospective clinical studies showed that clonal hematopoiesis (CH) was associated with stroke, and both were associated with inflammation. However, the relationship among CH, stroke, and inflammatory factors has not been systematically studied. We aim to use the Mendelian randomization (MR) method to study the relationship among them. In this study, the inverse-variance weighted method (IVW) was used as the main method, supplemented by other methods for MR analysis. Additionally, the sensitivity was tested by heterogeneity testing, pleiotropy testing, and leave-one-out analysis. This study used a variety of MR analysis methods to conclude that CH with variant allele fraction (VAF) ≥0.1 (CHLARGE) can increase the risk of cardioembolic stroke (CES) and proved the reliability of the results through sensitivity analysis. No causal relationship between other subtypes of CH and stroke was observed. Furthermore, while MR analysis demonstrated a causal link between both CH and stroke with inflammatory factors, specific inflammatory factors connecting CHLARGE with CES were not identified. Our study has confirmed the association among CH, stroke, and inflammatory factors. Additionally, we have identified CHLARGE as a risk factor for CES.