Study design: We investigated the effect of cerebrospinal fluid (CSF) haptoglobin perturbation on the risk of catastrophic aneurysmal subarachnoid haemorrhage (aSAH) using the Mendelian randomization framework in multi-ancestry and White British only populations.

As proof of concept, we explored the effect of genetically predicted plasma haptoglobin. To evaluate the specificity of this association, we investigated several related cerebrovascular traits as secondary outcomes. As sensitivity, we conducted colocalization analysis to assess whether CSF haptoglobin and catastrophic aSAH shared a causal variant.