BACKGROUND: Observational studies suggest an association between leukemia and stroke, but causality remains unclear. Certain leukemia types may increase stroke risk, but variations exist in stroke and mortality rates across leukemia subtypes. This study employed Mendelian randomization (MR) to investigate links between leukemia subtypes and stroke. METHODS: We conducted a two-sample Mendelian randomization (TSMR) study utilizing genetic variants linked to various subtypes of leukemia as instruments to investigate their causal effects on stroke, specifically ischemic stroke (IS) and intracerebral hemorrhage (ICH). The leukemia dataset comprised 456,276 subjects from the UK Biobank, while the stroke dataset was sourced from the FINNGEN consortium, encompassing 212,774 participants. RESULTS: In the present study, there was suggestive evidence that genetically predicted chronic lymphocytic leukemia (CLL) is associated with ischemic stroke (odds ratio, 1.02
95% confidence intervals, 1.01-1.05
P = 0.024), but no significant association was observed with intracerebral hemorrhage (ICH) (0.74
0.99-1.03
P = 0.237). Additionally, chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) was no significant associations between with stroke according to genetical prediction even if heterogeneity test and pleiotropic test was performed. CONCLUSIONS: Our Mendelian randomization analysis revealed that chronic lymphocytic leukemia (CLL) was associated with an increased risk of ischemic stroke (IS) but not intracerebral hemorrhage (ICH). Conversely, there was no evidence supporting causal associations of chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), or acute myeloid leukemia (AML) with either type of stroke. These findings enhance our comprehension of the intricate interplay between various leukemia subtypes and the risk of stroke. Further research is essential to delve into the underlying mechanisms and potential clinical implications of these observed associations.