Mendelian Randomization Analyses Show an Ambiguous Association between Clonal Hematopoiesis of Indeterminate Potential and Alzheimer's Disease Risk

Our MR analyses using multiple CHIP categorizations and multiple AD datasets dispute the hypothesis that CHIP is protective against AD, with some findings indicating some CHIP isoforms instead may be an AD risk factor. Our polygenic risk score data further indicates a possible confounding effect of CHIP by APOE genotype which in combination with varying age distributions in many AD datasets, may impact associations reported from previous longitudinal studies. While some CHIP isoforms may indeed be protective for AD, more work is needed to dissect the heterogeneity of CHIP and its relationship to AD risk.